POLYMORPHONUCLEAR NEUTROPHILS FROM HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS SHOW ENHANCED ACTIVATION, DIMINISHED FMLP-INDUCED L-SELECTIN SHEDDING, AND AN IMPAIRED OXIDATIVE BURST AFTER CYTOKINE PRIMING

Impaired polymorphonuclear neutrophil (PMN) function may contribute to the onset of certain life-threatening bacterial and fungal infections in human immunodeficiency virus (HIV)-infected patients. Published da ta on PMN functional activity in HIV infection are controversial, poss ibly because most studies have involved PMNs isolated from their blood environment by means of various procedures that may differently affec t surface receptor expression and thereby alter cellular responses. We therefore used flow cytometry to study the expression of adhesion mol ecules at the PMN surface, actin polymerization, and the oxidative bur st of whole-blood polymorphonuclear neutrophils in 42 HIV-infected pat ients at different stages of the disease. These PMNs were activated in vivo, as demonstrated by increased expression of the adhesion molecul e CD11b/CD18, reduced L-selectin antigen expression, increased actin p olymerization, and increased H2O2 production. The alterations were pre sent in asymptomatic patients with CD4(+) cell counts greater than 500 /mu L and did not increase with the progression of the disease. stimul ation by bacterial N-formyl peptides showed dysregulation of L-selecti n shedding end decreased H2O2 production after ex vivo priming with tu mor necrosis factor alpha or interleukin-8 (IL-8). These latter impair ments, which correlated with the decrease in CD4(+) lymphocyte numbers and with IL-8 and IL-6 plasma levels, could contribute to the increas ed susceptibility of HIV-infected patients to bacterial infections. (C ) 1994 by The American Society of Hematology.