Upregulation of Mac-1 on polymorphonuclear leukocytes (PMNS) by IL-8 produced by RSV- infected pulmonary epithelium

N. Nakajima, E. Molina, Z. Jiang, Janak Patel

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Abstract

Bronchoalveolar lavage of children and animals with RSV infection of the lower respiratory tract predominantly contains PMNs. However, the mechanism of migration of PMNs towards the RSV- infected epithelium is unknown. We have shown that RSV-infected respiratory epithelium produces IL-8, a potent chemotactic cytokine that also enhances adhesion of PMNs. IL-8 increases the surface expresssion of Mac-1 (CD11b/CD18) of PMNs, which in turn is utilized for adhesion-based migration. In the present study, the effect of RSV-induced IL-8 in regulation of PMN adherence molecule Mac-1 (CD11b/CD18) was evaluated. Supematants of RSV- infected A549 cells or 0.3 ug/ml of rlL-8 were incubated with neutralizing anti-IL-8 antibody (Ab) or conrol Ab for 2 h. 5 × 105 of human PMNs obtained from a healthy donor were incubated with these suspensions for 45 min. The PMNs were then stained with FITC-conjugated anti-Mac-1 antibody and were analyzed by flow cytometry. The results are expressed as percent change in mean fluorescence when compared with sham infection (control expresssed as 0%). %Change in Mac-1 rIL-8 + control Ab 43 ± 2 rIL-8 + IL-8 Ab 9 ± 2 RSV + control Ab 50 ± 1 RSV+IL-8 Ab 14±1 On PMNs incubated with RSV supernatants or rIL-8, the expression of Mac-1 significantly increased when compared with PMNs incubated with control media (p < 0.005). On the other hand, IL-8 Ab blocked the increase in Mac-1 expression due to RSV supematants or rIL-8 These results indicated that IL-8, released from RSV-infected epithelial cells, is the predominant mediator that modulates the surface expression of Mac-1 on PMNs. IL-8, therefore, is likely to play a major role in the PMN-induced inflammation during RSV infection.

Original languageEnglish (US)
JournalJournal of Investigative Medicine
Volume44
Issue number1
StatePublished - 1996

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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