Surfactant Protein A Enhances Alveolar Macrophage Phagocytosis of Apoptotic Neutrophils

Abstract

Surfactant protein A (SP-A) is an innate immune molecule that binds foreign organisms that invade the lungs and targets them for phagocytic clearance by the resident pulmonary phagocyte, the alveolar macrophage (AM). We hypothesized that SP-A binds to and enhances macrophage uptake of other nonself particles, specifically apoptotic polymorphonuclear neutrophils (PMNs). PMNs are recruited into the lungs during inflammation, but as inflammation is resolved, PMNs undergo apoptosis and are phagocytosed by AMs. We determined that SP-A increases AM phagocytosis of apoptotic PMNs 280 ± 62% above the no protein control value. The increase is dose dependent, and heat-treated SP-A still enhanced uptake, whereas deglycosylated SP-A had significantly diminished ability to enhance phagocytosis. Surfactant protein D also increased phagocytosis of apoptotic PMNs by ∼125%. However, other proteins that are structurally homologous to SP-A, mannose-binding lectin and complement protein 1q, did not. SP-A enhances phagocytosis via an opsonization-dependent mechanism and binds apoptotic PMNs ∼4-fold more than viable PMNs. Also, binding of SP-A to apoptotic PMNs does not appear to involve SP-A’s lectin domain. These data suggest that the pulmonary collectins SP-A and SP-D facilitate the resolution of inflammation by accelerating apoptotic PMN clearance.

The complement protein properdin binds apoptotic T cells and promotes complement activation and phagocytosis

“…During apoptosis, cells express new surface proteins and undergo reorientation of membrane phospholipids resulting in the surface exposure of phosphatidylserine (7,8). Phagocytes harbor receptors that can interact either directly with the altered apoptotic cell surface (8)(9)(10) or via receptors for soluble proteins that bind to apoptotic cells (5,11,12). Engagement of phagocyte receptors through these direct or indirect mechanisms induces the uptake of bound apoptotic cells (5,6).…”

Cytologic Features Оf Bronchoalveolar Lavage in Evaluation of Course of Exogenous Allergic Alveolitis

“…Содержание таких макрофагов варьировало у разных больных и было характерной особенностью этого вари-анта заболевания. При подостром и хроническом развитии воспаления в БАЛ появлялось небольшое число эпите-лиоидноподобных клеток, которые после электронно-микроскопического анализа были идентифицированы как гистиоциты с ультраструктурными признаками фаго-цитарной и секреторной способности [12]. В нашем исследовании к таким клеткам со смешанной функцией были отнесены макрофаги с гомогенной серовато-синей цитоплазмой без крупных включений или с единич-ными небольшими вакуолями, тогда как основной объем фагоцитоза выполняется альвеолярными макрофагами, в фагосомах которых чаще всего можно видеть целые лимфоциты, их фрагменты и апоптозные тельца.…”

Surface-bound myeloperoxidase is a ligand for recognition of late apoptotic neutrophils by human lung surfactant proteins A and D

“…Recognition and clearance of apoptotic cells are accomplished by a redundant system of phagocyte receptors Ogden et al, 2001;Somersan and Bhardwaj, 2001), soluble bridging molecules (Somersan and Bhardwaj, 2001), and apoptotic cell ligands (Fadok et al, 1992;Somersan and Bhardwaj, 2001). Evidence indicates that two members of the collectin family, surfactant protein A (SP-A) and surfactant protein D (SP-D), participate in apoptotic cell removal by alveolar macrophages in vitro (Schagat et al, 2001).…”