Complement C5a receptors in the pituitary gland: expression and function.
Communication between the immune and endocrine system is important for the control of inflammation that is primarily mediated through the hypothalamic-pituitary-adrenal axis. The innate immune system rapidly responds to pathogens by releasing complement proteins that include the anaphylatoxins C3a and C5a. We previously reported the existence of C3a receptors in the anterior pituitary gland and now describe the presence of C5a receptors in the gland. C5a and its less active derivative (C5adR) can bind to its own receptor and to another receptor called C5L2. Using RT-PCR and immunocytochemistry, C5a receptors and C5L2 were demonstrated in the rat anterior pituitary gland and in several rodent anterior pituitary cell lines. Western blotting analysis showed that C5a stimulated the phosphorylation of MAPK and AKT but not p38; C5adR on the other hand, had no effect on any of the signal molecules investigated. The effects of C5a and C5adR on the secretion of the inflammatory molecule, macrophage migration inhibitory factor (MIF) were investigated by ELISA. Both compounds showed a dose-dependent inhibition of MIF release, 30-40% inhibition at around 35-70 nM agonist with IC50 values of around 20 nM. C5a and C5adR also stimulated ACTH secretion (up to 25%) from AtT-20DV16 cells. These data show that functional C5a receptors (C5a and C5L2) are present in the anterior pituitary gland and they may play a role in dampening down inflammation by inhibiting the release of MIF and stimulating the release of ACTH.
Francis
Karen
K
Centre for Endocrine and Diabetes Sciences, Cardiff University, Cardiff, CF14 4XN, UK.
Lewis
B Mary
BM
Monk
Peter N
PN
Ham
Jack
J
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D015936:Complement C5a / Q000494:pharmacology; D015937:Complement C5a, des-Arginine / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D007155:Immunologic Factors / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008297:Male; D051379:Mice; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D044087:Receptor, Anaphylatoxin C5a / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
C000594938:C5ar2 protein, mouse; C496868:C5ar2 protein, rat; D015937:Complement C5a, des-Arginine; D007155:Immunologic Factors; D008263:Macrophage Migration-Inhibitory Factors; D044087:Receptor, Anaphylatoxin C5a; D019707:Receptors, Chemokine; D015936:Complement C5a; D000324:Adrenocorticotropic Hormone