Am. J. Respir. Cell Mol. Biol., Vol 11, No. 5, Nov 1994, 607-614.
Intrapulmonary antigen deposition in the human lung: local responses
DN Weissman, DE Bice, RE Crowell and MR Schuyler
West Virginia University School of Medicine, Morgantown.
We hypothesized that, as in animal models, localized deposition of antigen
into the human lung would induce local inflammatory and immune responses in
antigen-exposed sites. To test this hypothesis, segmental instillation of a
well-characterized, highly immunogenic, soluble antigen, keyhole limpet
hemocyanin (KLH) was performed in 10 healthy, nonsmoking volunteers. Ten to
fifteen days after instillation, bronchoalveolar lavage (BAL) was performed
in immunized segments (IS) and contralateral control segments (CS) and
local responses to antigen instillation were assessed by comparing IS and
CS BAL. Greater albumin concentrations and cell recoveries were found in IS
than in CS BAL, suggesting local inflammation. Although total numbers of
each cell type were increased, relative proportions of alveolar
macrophages, lymphocytes, and neutrophils were similar in IS and CS BAL.
CD4/CD8 ratios in IS BAL samples were greater than those in CS samples,
because of higher numbers of CD4+ lymphocytes in IS than in CS BAL but
similar numbers of CD8+ lymphocytes. Anti-KLH IgG and IgA concentrations
were greater in IS than in CS BAL. However, anti-KLH IgG/albumin ratios
were similar in IS BAL and serum, suggesting that anti-KLH IgG had reached
IS by passive transudation from the circulation. In contrast, anti-KLH
IgA/albumin concentrations were greater in IS BAL than in serum, suggesting
local production, and/or active transport of serum-derived anti-KLH IgA
into the IS. Fractionation of serum and IS BAL on sucrose gradients
demonstrated that anti-KLH IgA activity was largely associated with 11S
polymeric IgA in both locations.(ABSTRACT TRUNCATED AT 250 WORDS)