Impairment of HIV polymorphonuclear leukocyte transmigration across T84 cell monolayers: an alternative mechanisms for increased intestinal bacterial infections in AIDS?
Our objective was to study the influence of HIV infection of polymorphonuclear leukocytes (PMN) on transepithelial migration. To date, reports of functional PMN chemotaxis in AIDS are contradictory. This is the first attempt to assess this function via an in vitro model allowing transmigration of neutrophils through an intestinal epithelial barrier. PMN were isolated from 45 HIV-infected patients and 45 healthy volunteers. PMN transmigration across T84 epithelial cells was initiated by applying either various concentrations of formyl-met-leu-phe peptide (f-MLP) or interleukin-8 and assayed by quantification of myeloperoxidase activity. CD11b, CD18, and CD47 expression on PMN was compared before and after transepithelial migration by flow cytometry analysis. CD11b expression was studied by electron microscopy. Apoptosis of transmigrated HIV PMN and control PMN was investigated by morphology and DNA fragmentation characterization. Compared to control PMN, HIV PMN exhibited a decrease in transepithelial migration that directly correlated with CD4+ counts. Basal and transepithelial migration-mediated expression of CD11b, CD18, and CD47 were unmodified in HIV PMN compared to control PMN. Electron microscopy labeling confirmed no difference in CD11b expression on HIV and control PMN. The index of apoptosis in transmigrated HIV PMN and control PMN was identical. These data provide evidence of a defect in the f-MLP-induced chemotaxis of PMN from HIV-infected patients across an intestinal epithelial barrier. This defective migration is not due to a quantitative modification of CD11b, CD18 and CD47 on HIV PMN suggesting a more subtle alteration. The impairment in the transmigration function may contribute in vivo to an increased susceptibility to intestinal bacterial infection in HIV-infected patients.
Hofman
P
P
INSERM U. 364, Faculté de Médecine, avenue de Valombrose, 06107 Nice Cedex 01, France. hofman@unice.fr
Fischer
F
F
Far
D F
DF
Selva
E
E
Battaglione
V
V
Bayle
J
J
Rossi
B
B
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001424:Bacterial Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology; D007410:Intestinal Diseases / Q000150:complications / Q000276:immunology* / Q000473:pathology; D016177:Macrophage-1 Antigen / Q000276:immunology; D008297:Male; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology*
D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D009240:N-Formylmethionine Leucyl-Phenylalanine