Enhancement by tumor necrosis factor-alpha of Fc alpha receptor expression and IgA-mediated superoxide generation and killing of Pseudomonas aeruginosa by polymorphonuclear leukocytes.
Polymorphonuclear leukocytes (PMNL) in bronchoalveolar lavage (BAL) fluid of cystic fibrosis patients express increased levels of receptor for the Fc portion of IgA (Fc alpha R), similar to those found on PMNL stimulated with FMLP in vitro. Since tumor necrosis factor-alpha (TNF alpha) is an activator of PMNL and is found at inflammatory sites, its effects on Fc alpha R expression and IgA-mediated PMNL functions were investigated. Exposure of PMNL to TNF alpha increased surface expression of Fc alpha R 2- to 3-fold, increased superoxide production in response to aggregated IgA 5-fold, and increased phagocytosis of IgA aggregates 3- to 4-fold. Interleukin-8 did not increase Fc alpha R expression and did not enhance IgA-mediated superoxide generation. IgA-dependent PMNL killing of Pseudomonas aeruginosa was enhanced when PMNL were pretreated with TNF alpha. Thus, interactions between phagocytic host defense mechanisms and mucosal IgA may be enhanced by TNF alpha in the inflammatory milieu of the cystic fibrosis lung.
Dept. of Pediatrics, Case Western Reserve University, Cleveland, OH 44106.
R W
RW
Hostoffer
I
I
Krukovets
M
M
Berger
D000293:Adolescent; D000328:Adult; D003550:Cystic Fibrosis / Q000150:complications / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D016209:Interleukin-8 / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis; D011552:Pseudomonas Infections / Q000150:complications / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D011961:Receptors, Fc / Q000096:biosynthesis*; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D016209:Interleukin-8; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides