Binding of surfactant protein A to C1q receptors mediates phagocytosis of Staphylococcus aureus by monocytes.
During both steady-state conditions and inflammatory reactions in the lower airways, monocytes migrate to the alveoli where they come into contact with surfactant. Surfactant is composed of phospholipids, neutral lipids, and specific proteins, and its main function is to reduce surface tension in the alveoli. The most abundant glycoprotein surfactant protein A (SP-A) affects the structure, function, and metabolism of pulmonary surfactant. The aim of the present study was to determine whether SP-A plays a role in the antibacterial activities of human monocytes and whether this is mediated by a receptor for SP-A on these cells. The results showed that SP-A binds to both Staphylococcus aureus and monocytes and mediates the phagocytosis of the bacteria by these cells. SP-A does not stimulate the intracellular killing of bacteria by monocytes, and SP-A-opsonized S. aureus do not induce the production of reactive oxygen intermediates. SP-A binds to the C1q receptor (C1qR) on monocytes, since its binding was inhibited by C1q and the SP-A-enhanced association of S. aureus with these cells was completely abolished when monocytes were adherent to surfaces coated with C1q or anti-C1qR monoclonal antibody. Furthermore, the binding of SP-A to monocytes results in an increased intracellular concentration of adenosine 3',5'-cyclic monophosphate. Together, these results demonstrate that C1qR mediates the phagocytosis of SP-A-opsonized S. aureus by monocytes.
Department of Infectious Diseases, University Hospital Leiden, The Netherlands.
M F
MF
Geertsma
P H
PH
Nibbering
H P
HP
Haagsman
M R
MR
Daha
R
R
van Furth
D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors; D006861:Hydrogen Peroxide / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D009000:Monocytes / Q000502:physiology*; D009895:Opsonin Proteins / Q000494:pharmacology; D009994:Osmolar Concentration; D010587:Phagocytosis / Q000502:physiology*; D011510:Proteolipids / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism*; D011951:Receptors, Complement / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects
C087299:C1QBP protein, human; D002352:Carrier Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D024101:Mitochondrial Proteins; D009895:Opsonin Proteins; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D011951:Receptors, Complement; C032402:complement 1q receptor; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D002118:Calcium