Surfactant protein A modulates release of reactive oxygen species from alveolar macrophages

Abstract

The production and release of reactive oxygen species (the respiratory burst) is a common metabolic pathway linked to several macrophage-related reactions. The most abundant surfactant protein A (SP-A) binds to alveolar macrophages (AM) through a specific surface receptor with high affinity. Because such binding might initiate or modulate the respiratory burst, we wanted to know whether and how SP-A affects the oxygen radical release from AM. To answer these questions, we measured the release of reactive oxygen species from rat AM under various in vitro conditions using enhanced chemiluminescence systems. We prepared SP-A from pulmonary surfactant isolated either from silica-treated rats or adult dogs. Resident AM were harvested from pathogen-free Wistar rats by lung lavage. Adhered and nonadhered AM were assessed on protein-free or protein-coated surfaces of 96-well microtiter plates. On protein-free surfaces, the sole addition of SP-A failed to induce measurable oxygen radical release from 2 x 10(5) adhered or nonadhered AM, while zymosan opsonized with SP-A induced a marked increase over control. On protein-coated surfaces, AM respond differently depending on the coated protein: on SP-A-coated surfaces, a dose-dependent enhancement of oxygen radical release with a mean effective concentration of approximately 1.15 micrograms/ml was found. No such enhancement was seen on plates coated with similar amounts of either human fibronectin or collagen, and the enhancement with serum albumin was not dose related. Our data demonstrate that SP-A only enhances oxygen radical release from AM if SP-A is fixed to zymosan or the surface of the reaction vial in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

The Pulmonary Surfactant System: Biochemical and Clinical Aspects

“…The SP-A-induced stimulation of superoxide radical production is not observed with peritoneal macrophages, polymorphonuclear leukocytes, or monocytes [320]. SP-A surface interactions are required to release oxygen radicals from alveolar macrophages in vitro [342].…”

Interaction of human lung surfactant proteins A and D with mite (Dermatophagoides pteronyssinus) allergens

“…In addition to the regulatory function of these proteins in surfactant phospholipid metabolism, there is increasing evidence that they may also contribute to primary host-defence mechanisms in the lung [3]. The hydrophilic SP-A and SP-D can interact with lipopolysaccharides (LPS) from Gram-negative bacteria, facilitate opsonization, and enhance the respiratory burst of alveolar macrophages [4][5][6][7]. SP-A and SP-D along with several serum proteins, mannan-binding protein (MBP), bovine conglutinin and collectin-43, form the group of C-type lectins known as the collectins [8] which are characterized by having polypeptide chains composed of a short, cysteine-rich, N-terminal section followed by a collagen-like region, an -helical section and a Cterminal carbohydrate recognition domain (CRD) [9].…”

Surfactant apoprotein A modulates interleukin-8 and monocyte chemotactic peptide-1 production

“…Recent reports focused on immunoregulatory functions of SP-A, mostly directed towards monocytes and macrophages [5][6][7][8][9][10][11][12][13][14][15][16][17]. SP-A can stimulate macrophage antibacterial functions, in particular phagocytosis of several bacteria [8][9][10][11]14] including Mycobacterium tuberculosis [6].…”

“…Several functions have been attributed to SP-A, including the modulation of defence against pathogens [3,4]. In fact, SP-A enhances attachment [5][6][7], chemotaxis, phagocytosis, and oxygen-dependent killing [8][9][10][11][12][13][14] of specific respiratory pathogens in monocytes and alveolar macrophages. In addition, SP-A stimulates the production of many pro-inflammatory cytokines by human type-II cells or monocytes [15,16] and the release of tumour necrosis factor (TNF)-a, interleukin (IL)-1b, IL-6 and IL-8 by the monocytic THP-1 cell line [17].…”