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14 pages, 3139 KiB

Open AccessArticle

ATP Consumption Is Coupled with Endocytosis in Exudated Neutrophils

by Duo Wang, Zirui Zeng, Mengyue Shen, Ryuji Okazaki, Hironori Miyata, Tomo Yonezawa and Yasuhiro Yoshida

Int. J. Mol. Sci. 2023, 24(10), 9039; https://doi.org/10.3390/ijms24109039 - 20 May 2023

Cited by 1 | Viewed by 1393

Abstract

Neutrophil energy metabolism during phagocytosis has been previously reported, and adenosine triphosphate (ATP) plays a crucial role in endocytosis. Neutrophils are prepared by intraperitoneal injection of thioglycolate for 4 h. We previously reported a system established for measuring particulate matter endocytosis by neutrophils [...] Read more.

Neutrophil energy metabolism during phagocytosis has been previously reported, and adenosine triphosphate (ATP) plays a crucial role in endocytosis. Neutrophils are prepared by intraperitoneal injection of thioglycolate for 4 h. We previously reported a system established for measuring particulate matter endocytosis by neutrophils using flow cytometry. In this study, we utilized this system to investigate the relationship between endocytosis and energy consumption in neutrophils. A dynamin inhibitor suppressed ATP consumption triggered by neutrophil endocytosis. In the presence of exogenous ATP, neutrophils behave differently during endocytosis depending on ATP concentration. The inhibition of ATP synthase and nicotinamide adenine dinucleotide phosphate oxidase but not phosphatidylinositol-3 kinase suppresses neutrophil endocytosis. The nuclear factor kappa B was activated during endocytosis and inhibited by I kappa B kinase (IKK) inhibitors. Notably, IKK inhibitors restored endocytosis-triggered ATP consumption. Furthermore, data from the NLR family pyrin domain containing three knockout mice suggest that inflammasome activation is not involved in neutrophil endocytosis or concomitant ATP consumption. To summarize, these molecular events occur via endocytosis, which is closely related to ATP-centered energy metabolism. Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

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17 pages, 1719 KiB

Open AccessArticle

Redox-Activation of Neutrophils Induced by Pericardium Scaffolds

by Irina I. Vlasova, Shakir K. Suleimanov, Elena V. Mikhalchik, Nailya T. Urmantaeva, Emin L. Salimov, Aligeydar A. Ragimov, Tatyana M. Khlebnikova and Peter S. Timashev

Int. J. Mol. Sci. 2022, 23(24), 15468; https://doi.org/10.3390/ijms232415468 - 07 Dec 2022

Cited by 2 | Viewed by 1260

Abstract

Implantation of scaffolds causes a local inflammatory response whereby the early recruitment of neutrophils is of great importance not only for fighting the infection, but also for facilitating effective regeneration. We used luminol-dependent chemiluminescence, flow cytometry, ELISA, and confocal microscopy to assess the [...] Read more.

Implantation of scaffolds causes a local inflammatory response whereby the early recruitment of neutrophils is of great importance not only for fighting the infection, but also for facilitating effective regeneration. We used luminol-dependent chemiluminescence, flow cytometry, ELISA, and confocal microscopy to assess the responses of neutrophils after the exposure to the scaffold-decellularized bovine pericardium (collagen type I) crosslinked with genipin (DBPG). We demonstrated that DBPG activated neutrophils in whole blood causing respiratory burst, myeloperoxidase (MPO) secretion, and formation of neutrophil extracellular trap-like structures (NETs). In addition, we studied platelets, another important player of the immediate immune host response. We found that platelets triggered redox-activation of isolated neutrophils by the pericardium scaffold, and likely participate in the NETs formation. Free radicals generated by neutrophils and hypochlorous acid produced by MPO are potent oxidizing agents which can oxidatively degrade biological structures. Understanding the mechanisms and consequences of redox activation of neutrophils by pericardium scaffolds is important for the development of new approaches to increase the efficiency of tissue regeneration. Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

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15 pages, 1317 KiB

Open AccessArticle

High-Density Lipoprotein Suppresses Neutrophil Extracellular Traps Enhanced by Oxidized Low-Density Lipoprotein or Oxidized Phospholipids

by Hitomi Ohinata, Takashi Obama, Tomohiko Makiyama, Yuichi Watanabe and Hiroyuki Itabe

Int. J. Mol. Sci. 2022, 23(22), 13992; https://doi.org/10.3390/ijms232213992 - 13 Nov 2022

Cited by 3 | Viewed by 1607

Abstract

Neutrophil extracellular traps (NETs) are found in patients with various diseases, including cardiovascular diseases. We previously reported that copper-oxidized low-density lipoprotein (oxLDL) promotes NET formation of neutrophils, and that the resulting NETs increase the inflammatory responses of endothelial cells. In this study, we [...] Read more.

Neutrophil extracellular traps (NETs) are found in patients with various diseases, including cardiovascular diseases. We previously reported that copper-oxidized low-density lipoprotein (oxLDL) promotes NET formation of neutrophils, and that the resulting NETs increase the inflammatory responses of endothelial cells. In this study, we investigated the effects of high-density lipoproteins (HDL) on NET formation. HL-60-derived neutrophils were treated with phorbol 12-myristate 13-acetate (PMA) and further incubated with oxLDL and various concentrations of HDL for 2 h. NET formation was evaluated by quantifying extracellular DNA and myeloperoxidase. We found that the addition of native HDL partially decreased NET formation of neutrophils induced by oxLDL. This effect of HDL was lost when HDL was oxidized. We showed that oxidized phosphatidylcholines and lysophosphatidylcholine, which are generated in oxLDL, promoted NET formation of PMA-primed neutrophils, and NET formation by these products was completely blocked by native HDL. Furthermore, we found that an electronegative subfraction of LDL, LDL(–), which is separated from human plasma and is thought to be an in vivo oxLDL, was capable of promoting NET formation. These results suggest that plasma lipoproteins and their oxidative modifications play multiple roles in promoting NET formation, and that HDL acts as a suppressor of this response. Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

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11 pages, 328 KiB

Open AccessArticle

Blood Cell Responses Following Heavy Alcohol Consumption Coincide with Changes in Acute Phase Reactants of Inflammation, Indices of Hemolysis and Immune Responses to Ethanol Metabolites

by Onni Niemelä, Anni S. Halkola, Aini Bloigu, Risto Bloigu, Ulla Nivukoski, Heidi Pohjasniemi and Johanna Kultti

Int. J. Mol. Sci. 2022, 23(21), 12738; https://doi.org/10.3390/ijms232112738 - 22 Oct 2022

Cited by 2 | Viewed by 2717

Abstract

Aberrations in blood cells are common among heavy alcohol drinkers. In order to shed further light on such responses, we compared blood cell status with markers of hemolysis, mediators of inflammation and immune responses to ethanol metabolites in alcohol-dependent patients at the time [...] Read more.

Aberrations in blood cells are common among heavy alcohol drinkers. In order to shed further light on such responses, we compared blood cell status with markers of hemolysis, mediators of inflammation and immune responses to ethanol metabolites in alcohol-dependent patients at the time of admission for detoxification and after abstinence. Blood cell counts, indices of hemolysis (LDH, haptoglobin, bilirubin), calprotectin (a marker of neutrophil activation), suPAR, CD163, pro- and anti-inflammatory cytokines and autoantibodies against protein adducts with acetaldehyde, the first metabolite of ethanol, were measured from alcohol-dependent patients (73 men, 26 women, mean age 43.8 ± 10.4 years) at baseline and after 8 ± 1 days of abstinence. The assessments also included information on the quantities of alcohol drinking and assays for biomarkers of alcohol consumption (CDT), liver function (AST, ALT, ALP, GGT) and acute phase reactants of inflammation. At baseline, the patients showed elevated values of CDT and biomarkers of liver status, which decreased significantly during abstinence. A significant decrease also occurred in LDH, bilirubin, CD163 and IgA and IgM antibodies against acetaldehyde adducts, whereas a significant increase was noted in blood leukocytes, platelets, MCV and suPAR levels. The changes in blood leukocytes correlated with those in serum calprotectin (p < 0.001), haptoglobin (p < 0.001), IL-6 (p < 0.02) and suPAR (p < 0.02). The changes in MCV correlated with those in LDH (p < 0.02), MCH (p < 0.01), bilirubin (p < 0.001) and anti-adduct IgG (p < 0.01). The data indicates that ethanol-induced changes in blood leukocytes are related with acute phase reactants of inflammation and release of neutrophil calprotectin. The studies also highlight the role of hemolysis and immune responses to ethanol metabolites underlying erythrocyte abnormalities in alcohol abusers. Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

12 pages, 1206 KiB

Open AccessCommunication

Neutrophil Count as Atrioventricular Block (AVB) Predictor following Pediatric Heart Surgery

by Tomasz Urbanowicz, Anna Olasińska-Wiśniewska, Marcin Gładki, Michał Michalak, Mateusz Sochacki, Anita Weclewska, Dominika Zalas, Waldemar Bobkowski and Marek Jemielity

Int. J. Mol. Sci. 2022, 23(20), 12409; https://doi.org/10.3390/ijms232012409 - 17 Oct 2022

Cited by 3 | Viewed by 1335

Abstract

Neutrophils play a significant role in immune and inflammatory reactions. The preoperative inflammatory activation may have a detrimental effect on postoperative outcomes. The aim of the study was to investigate the relation between preoperative hematological indices on postoperative complications’ risk in pediatric cardiac [...] Read more.

Neutrophils play a significant role in immune and inflammatory reactions. The preoperative inflammatory activation may have a detrimental effect on postoperative outcomes. The aim of the study was to investigate the relation between preoperative hematological indices on postoperative complications’ risk in pediatric cardiac congenital surgery. The retrospective single center analysis included 93 pediatric patients (48 (65%) males and 45 (35%) females), mean age of 7 (3–30) months referred for cardiac surgery in cardiopulmonary bypass due to functional single ventricle disease (26 procedures), shunts lesions (40 procedures) and cyanotic disease (27 procedures). Among simple hematological indices, the receiver-operating-characteristic curve showed that a neutrophil count below 2.59 K/uL was found as an optimal cut-off point for predicting postoperative atrioventricular block following pediatric cardiac surgery (AUC = 0.845, p < 0.0001) yielding a sensitivity of 100% and a specificity of 65.62%. Preoperative values of neutrophil count below 2.59 K/uL in whole blood analysis can be regarded as a predictive factor (AUC = 0.845, p < 0.0001) for postoperative atrioventricular block in pediatric cardiac surgery. Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

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16 pages, 1695 KiB

Open AccessArticle

Activation of Neutrophils by Mucin–Vaterite Microparticles

by Elena Mikhalchik, Liliya Yu. Basyreva, Sergey A. Gusev, Oleg M. Panasenko, Dmitry V. Klinov, Nikolay A. Barinov, Olga V. Morozova, Alexander P. Moscalets, Liliya N. Maltseva, Lyubov Yu. Filatova, Evgeniy A. Pronkin, Julia A. Bespyatykh and Nadezhda G. Balabushevich

Int. J. Mol. Sci. 2022, 23(18), 10579; https://doi.org/10.3390/ijms231810579 - 13 Sep 2022

Cited by 3 | Viewed by 2409

Abstract

Nano- and microparticles enter the body through the respiratory airways and the digestive system, or form as biominerals in the gall bladder, salivary glands, urinary bladder, kidney, or diabetic pancreas. Calcium, magnesium, and phosphate ions can precipitate from biological fluids in the presence [...] Read more.

Nano- and microparticles enter the body through the respiratory airways and the digestive system, or form as biominerals in the gall bladder, salivary glands, urinary bladder, kidney, or diabetic pancreas. Calcium, magnesium, and phosphate ions can precipitate from biological fluids in the presence of mucin as hybrid nanoparticles. Calcium carbonate nanocrystallites also trap mucin and are assembled into hybrid microparticles. Both mucin and calcium carbonate polymorphs (calcite, aragonite, and vaterite) are known to be components of such biominerals as gallstones which provoke inflammatory reactions. Our study was aimed at evaluation of neutrophil activation by hybrid vaterite–mucin microparticles (CCM). Vaterite microparticles (CC) and CCM were prepared under standard conditions. The diameter of CC and CCM was 3.3 ± 0.8 µm and 5.8 ± 0.7 µm, with ƺ-potentials of −1 ± 1 mV and −7 ± 1 mV, respectively. CC microparticles injured less than 2% of erythrocytes in 2 h at 1.5 mg mL⁻¹, and no hemolysis was detected with CCM; this let us exclude direct damage of cellular membranes by microparticles. Activation of neutrophils was analyzed by luminol- and lucigenin-dependent chemiluminescence (Lum-CL and Luc-CL), by cytokine gene expression (IL-6, IL-8, IL-10) and release (IL-1β, IL-6, IL-8, IL-10, TNF-α), and by light microscopy of stained smears. There was a 10-fold and higher increase in the amplitude of Lum-CL and Luc-CL after stimulation of neutrophils with CCM relative to CC. Adsorption of mucin onto prefabricated CC microparticles also contributed to activation of neutrophil CL, unlike mucin adsorption onto yeast cell walls (zymosan); adsorbed mucin partially suppressed zymosan-stimulated production of oxidants by neutrophils. Preliminary treatment of CCM with 0.1–10 mM NaOCl decreased subsequent activation of Lum-CL and Luc-CL of neutrophils depending on the used NaOCl concentration, presumably because of the surface mucin oxidation. Based on the results of ELISA, incubation of neutrophils with CCM downregulated IL-6 production but upregulated that of IL-8. IL-6 and IL-8 gene expression in neutrophils was not affected by CC or CCM according to RT²-PCR data, which means that post-translational regulation was involved. Light microscopy revealed adhesion of CC and CCM microparticles onto the neutrophils; CCM increased neutrophil aggregation with a tendency to form neutrophil extracellular traps (NETs). We came to the conclusion that the main features of neutrophil reaction to mucin–vaterite hybrid microparticles are increased oxidant production, cell aggregation, and NET-like structure formation, but without significant cytokine release (except for IL-8). This effect of mucin is not anion-specific since particles of powdered kidney stone (mainly calcium oxalate) in the present study or calcium phosphate nanowires in our previous report also activated Lum-CL and Luc-CL response of neutrophils after mucin sorption. Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

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11 pages, 1428 KiB

Open AccessArticle

Circulating Ageing Neutrophils as a Marker of Asymptomatic Polyvascular Atherosclerosis in Statin-Naïve Patients without Established Cardiovascular Disease

by Vadim Genkel, Ilya Dolgushin, Irina Baturina, Albina Savochkina, Karina Nikushkina, Anna Minasova, Lubov Pykhova, Veronika Sumerkina, Alla Kuznetsova and Igor Shaposhnik

Int. J. Mol. Sci. 2022, 23(17), 10195; https://doi.org/10.3390/ijms231710195 - 05 Sep 2022

Cited by 1 | Viewed by 1675

Abstract

Background: Current data on the possible involvement of aging neutrophils in atherogenesis are limited. This study aimed to research the diagnostic value of aging neutrophils in their relation to subclinical atherosclerosis in statin-naïve patients without established atherosclerotic cardiovascular diseases (ASCVD). Methods: The study [...] Read more.

Background: Current data on the possible involvement of aging neutrophils in atherogenesis are limited. This study aimed to research the diagnostic value of aging neutrophils in their relation to subclinical atherosclerosis in statin-naïve patients without established atherosclerotic cardiovascular diseases (ASCVD). Methods: The study was carried out on 151 statin-naïve patients aged 40–64 years old without ASCVD. All patients underwent duplex scanning of the carotid arteries, lower limb arteries and abdominal aorta. Phenotyping and differentiation of neutrophil subpopulations were performed through flow cytometry (Navios 6/2, Beckman Coulter, USA). Results: The number of CD62L^loCXCR4^hi-neutrophils is known to be significantly higher in patients with subclinical atherosclerosis compared with patients without atherosclerosis (p = 0.006). An increase in the number of CD62L^loCXCR4^hi-neutrophils above cut-off values makes it possible to predict atherosclerosis in at least one vascular bed with sensitivity of 35.4–50.5% and specificity of 80.0–92.1%, in two vascular beds with sensitivity of 44.7–84.4% and specificity of 80.8–33.3%. Conclusion: In statin-naïve patients 40–64 years old without established ASCVD with subclinical atherosclerosis, there is an increase in circulating CD62L^loCXCR4^hi-neutrophils. It was also concluded that the increase in the number of circulating CD62L^loCXCR4^hi-neutrophils demonstrated moderate diagnostic efficiency (AUC 0.617–0.656) in relation to the detection of subclinical atherosclerosis, including polyvascular atherosclerosis. Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

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14 pages, 2981 KiB

Open AccessArticle

Neutrophil Activation by Mineral Microparticles Coated with Methylglyoxal-Glycated Albumin

by Elena V. Mikhalchik, Victor A. Ivanov, Irina V. Borodina, Olga V. Pobeguts, Igor P. Smirnov, Irina V. Gorudko, Daria V. Grigorieva, Olga P. Boychenko, Alexander P. Moskalets, Dmitry V. Klinov, Oleg M. Panasenko, Luboff Y. Filatova, Ekaterina A. Kirzhanova and Nadezhda G. Balabushevich

Int. J. Mol. Sci. 2022, 23(14), 7840; https://doi.org/10.3390/ijms23147840 - 16 Jul 2022

Cited by 1 | Viewed by 1633

Abstract

Hyperglycemia-induced protein glycation and formation of advanced glycation end-products (AGEs) plays an important role in the pathogenesis of diabetic complications and pathological biomineralization. Receptors for AGEs (RAGEs) mediate the generation of reactive oxygen species (ROS) via activation of NADPH-oxidase. It is conceivable that [...] Read more.

Hyperglycemia-induced protein glycation and formation of advanced glycation end-products (AGEs) plays an important role in the pathogenesis of diabetic complications and pathological biomineralization. Receptors for AGEs (RAGEs) mediate the generation of reactive oxygen species (ROS) via activation of NADPH-oxidase. It is conceivable that binding of glycated proteins with biomineral particles composed mainly of calcium carbonate and/or phosphate enhances their neutrophil-activating capacity and hence their proinflammatory properties. Our research managed to confirm this hypothesis. Human serum albumin (HSA) was glycated with methylglyoxal (MG), and HSA-MG was adsorbed onto mineral microparticles composed of calcium carbonate nanocrystals (vaterite polymorph, CC) or hydroxyapatite nanowires (CP). As scopoletin fluorescence has shown, H₂O₂ generation by neutrophils stimulated with HSA-MG was inhibited with diphenyleneiodonium chloride, wortmannin, genistein and EDTA, indicating a key role for NADPH-oxidase, protein tyrosine kinase, phosphatidylinositol 3-kinase and divalent ions (presumably Ca²⁺) in HSA-MG-induced neutrophil respiratory burst. Superoxide anion generation assessed by lucigenin-enhanced chemiluminescence (Luc-CL) was significantly enhanced by free HSA-MG and by both CC-HSA-MG and CP-HSA-MG microparticles. Comparing the concentrations of CC-bound and free HSA-MG, one could see that adsorption enhanced the neutrophil-activating capacity of HSA-MG. Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

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19 pages, 6419 KiB

Open AccessArticle

Low Concentration of the Neutrophil Proteases Cathepsin G, Cathepsin B, Proteinase-3 and Metalloproteinase-9 Induce Biofilm Formation in Non-Biofilm-Forming Staphylococcus epidermidis Isolates

by Itzia S. Gómez-Alonso, Sergio Martínez-García, Gabriel Betanzos-Cabrera, Esmeralda Juárez, María C. Sarabia-León, María Teresa Herrera, Fernando Gómez-Chávez, Luvia Sanchez-Torres, Sandra Rodríguez-Martínez, Mario E. Cancino-Diaz, Jorge Cancino and Juan C. Cancino-Diaz

Int. J. Mol. Sci. 2022, 23(9), 4992; https://doi.org/10.3390/ijms23094992 - 30 Apr 2022

Cited by 3 | Viewed by 2045

Abstract

Neutrophils play a crucial role in eliminating bacteria that invade the human body; however, cathepsin G can induce biofilm formation in a non-biofilm-forming Staphylococcus epidermidis 1457 strain, suggesting that neutrophil proteases may be involved in biofilm formation. Cathepsin G, cathepsin B, proteinase-3, and [...] Read more.

Neutrophils play a crucial role in eliminating bacteria that invade the human body; however, cathepsin G can induce biofilm formation in a non-biofilm-forming Staphylococcus epidermidis 1457 strain, suggesting that neutrophil proteases may be involved in biofilm formation. Cathepsin G, cathepsin B, proteinase-3, and metalloproteinase-9 (MMP-9) from neutrophils were tested on the biofilm induction in commensal (skin isolated) and clinical non-biofilm-forming S. epidermidis isolates. From 81 isolates, 53 (74%) were aap⁺, icaA⁻, icaD⁻ genotype, and without the capacity of biofilm formation under conditions of 1% glucose, 4% ethanol or 4% NaCl, but these 53 non-biofilm-forming isolates induced biofilm by the use of different neutrophil proteases. Of these, 62.3% induced biofilm with proteinase-3, 15% with cathepsin G, 10% with cathepsin B and 5% with MMP -9, where most of the protease-induced biofilm isolates were commensal strains (skin). In the biofilm formation kinetics analysis, the addition of phenylmethylsulfonyl fluoride (PMSF; a proteinase-3 inhibitor) showed that proteinase-3 participates in the cell aggregation stage of biofilm formation. A biofilm induced with proteinase-3 and DNAse-treated significantly reduced biofilm formation at an early time (initial adhesion stage of biofilm formation) compared to untreated proteinase-3-induced biofilm (p < 0.05). A catheter inoculated with a commensal (skin) non-biofilm-forming S. epidermidis isolate treated with proteinase-3 and another one without the enzyme were inserted into the back of a mouse. After 7 days of incubation period, the catheters were recovered and the number of grown bacteria was quantified, finding a higher amount of adhered proteinase-3-treated bacteria in the catheter than non-proteinase-3-treated bacteria (p < 0.05). Commensal non-biofilm-forming S. epidermidis in the presence of neutrophil cells significantly induced the biofilm formation when multiplicity of infection (MOI) 1:0.01 (neutrophil:bacteria) was used, but the addition of a cocktail of protease inhibitors impeded biofilm formation. A neutrophil:bacteria assay did not induce neutrophil extracellular traps (NETs). Our results suggest that neutrophils, in the presence of commensal non-biofilm-forming S. epidermidis, do not generate NETs formation. The effect of neutrophils is the production of proteases, and proteinase-3 releases bacterial DNA at the initial adhesion, favoring cell aggregation and subsequently leading to biofilm formation. Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

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Review

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23 pages, 2192 KiB

Open AccessReview

The Importance of CXCL1 in the Physiological State and in Noncancer Diseases of the Oral Cavity and Abdominal Organs

by Jan Korbecki, Iwona Szatkowska, Patrycja Kupnicka, Wojciech Żwierełło, Katarzyna Barczak, Iwona Poziomkowska-Gęsicka, Jerzy Wójcik, Dariusz Chlubek and Irena Baranowska-Bosiacka

Int. J. Mol. Sci. 2022, 23(13), 7151; https://doi.org/10.3390/ijms23137151 - 28 Jun 2022

Cited by 13 | Viewed by 4446

Abstract

CXCL1 is a CXC chemokine, CXCR2 ligand and chemotactic factor for neutrophils. In this paper, we present a review of the role of the chemokine CXCL1 in physiology and in selected major non-cancer diseases of the oral cavity and abdominal organs (gingiva, salivary [...] Read more.

CXCL1 is a CXC chemokine, CXCR2 ligand and chemotactic factor for neutrophils. In this paper, we present a review of the role of the chemokine CXCL1 in physiology and in selected major non-cancer diseases of the oral cavity and abdominal organs (gingiva, salivary glands, stomach, liver, pancreas, intestines, and kidneys). We focus on the importance of CXCL1 on implantation and placentation as well as on human pluripotent stem cells. We also show the significance of CXCL1 in selected diseases of the abdominal organs, including the gastrointestinal tract and oral cavity (periodontal diseases, periodontitis, Sjögren syndrome, Helicobacter pylori infection, diabetes, liver cirrhosis, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), HBV and HCV infection, liver ischemia and reperfusion injury, inflammatory bowel disease (Crohn’s disease and ulcerative colitis), obesity and overweight, kidney transplantation and ischemic-reperfusion injury, endometriosis and adenomyosis). Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

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12 pages, 1740 KiB

Open AccessReview

Understanding the Role of LFA-1 in Leukocyte Adhesion Deficiency Type I (LAD I): Moving towards Inflammation?

by Julia Fekadu, Ute Modlich, Peter Bader and Shahrzad Bakhtiar

Int. J. Mol. Sci. 2022, 23(7), 3578; https://doi.org/10.3390/ijms23073578 - 25 Mar 2022

Cited by 7 | Viewed by 5651

Abstract

LFA-1 (Lymphocyte function-associated antigen-1) is a heterodimeric integrin (CD11a/CD18) present on the surface of all leukocytes; it is essential for leukocyte recruitment to the site of tissue inflammation, but also for other immunological processes such as T cell activation and formation of the [...] Read more.

LFA-1 (Lymphocyte function-associated antigen-1) is a heterodimeric integrin (CD11a/CD18) present on the surface of all leukocytes; it is essential for leukocyte recruitment to the site of tissue inflammation, but also for other immunological processes such as T cell activation and formation of the immunological synapse. Absent or dysfunctional expression of LFA-1, caused by mutations in the ITGB2 (integrin subunit beta 2) gene, results in a rare immunodeficiency syndrome known as Leukocyte adhesion deficiency type I (LAD I). Patients suffering from severe LAD I present with recurrent infections of the skin and mucosa, as well as inflammatory symptoms complicating the clinical course of the disease before and after allogeneic hematopoietic stem cell transplantation (alloHSCT); alloHSCT is currently the only established curative treatment option. With this review, we aim to provide an overview of the intrinsic role of inflammation in LAD I. Full article

(This article belongs to the Special Issue Neutrophil in Cell Biology and Diseases)

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