Vitronectin, fibronectin, and gp120 antibody enhance macrophage release of TNF-α in response to Pneumocystis carinii

Lewis W. Neese, Joseph E. Standing, Eric J. Olson, Mario Castro, Andrew H. Limper

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Alveolar macrophages (AMS) initiate inflammation during Pneumocystis carinii pneumonia by releasing cytokines including TNF-α. Recent studies suggest that macrophage responses to P. carinii are enhanced by serum opsonization, but the mechanisms of enhancement are not well defined. To determine whether macrophage release of TNF-α in response to P. carinii was augmented by immune opsonization, alveolar macrophages obtained from rabbits were cultured with P. carinii that had been opsonized with either nonimmune rabbit serum, immune serum generated against P. carinii, or an affinity- purified polyclonal Ab recognizing the major P. carinii surface Ag gp120. Each experiment also included organisms maintained in media alone (nonopsonized P. carinii). Opsonization of P. carinii with immune serum or gp120 Ab significantly enhanced macrophage TNF-α release. Interestingly, however, opsonization with nonimmune serum also increased TNF-α response to the organism. Because P. carinii is known to interact with the adhesive glycoproteins, vitronectin (VN) and fibronectin (FN), we hypothesized that they might also augment TNF-α release. Opsonization of P. carinii with VN or FN resulted in significant potentiation of macrophage TNF-α liberation. We further determined that VN and FN were present in increased quantities in the lower respiratory tract of patients with P. carinii pneumonia compared with normal volunteers. Additionally, VN and FN were demonstrated on the surface of freshly isolated P. carinii organisms by immunoblot analysis. Our study suggests that immune and nonimmune opsonins contribute to host defenses during P. carinii pneumonia by enhancing regional TNF-α release in response to the organism.

Original languageEnglish (US)
Pages (from-to)4549-4556
Number of pages8
JournalJournal of Immunology
Volume152
Issue number9
StatePublished - May 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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