Human mesangial cells in culture and in kidney sections fail to express Fc alpha receptor (CD89).
The mechanism of deposition of IgA in the renal mesangium in primary IgA-nephropathy is poorly understood. It has been suggested that membrane receptors for IgA on mesangial cells (MC) of the kidney may be involved. To obtain more insight in the occurrence of the myeloid receptor for IgA (CD89) on MC, both in situ and in culture, rabbit and goat polyclonal antibodies and mouse monoclonal antibody against recombinant CD89 were raised. Kidney sections from five control subjects and five patients with primary IgA-nephropathy failed to be positive for CD89 in the mesangium, using our polyclonal and monoclonal antibodies. Also, five primary human MC cultures assessed for CD89 expression showed no protein expression of CD89. Furthermore, reverse transcription-PCR failed to detect mRNA expression of CD89 in the cultured MC. It was demonstrated that all five human primary MC bound human IgA in a dose-dependent manner, which was not inhibitable by blocking monoclonal anti-CD89 antibody (My43). In contrast, binding of IgA to U937 cells was blocked efficiently by My43. Finally, incubation of human MC with either human or rat IgA led to increased interleukin-6 production, whereas only human IgA, but not rat IgA, was able to bind to human CD89. Therefore, it is concluded that human MC do not express CD89 (to a significant extent). These results strongly suggest that binding of IgA to human MC occurs via an IgA receptor distinct from CD89.
Westerhuis
R
R
Department of Nephrology, Leiden University Medical Center, The Netherlands.
Van Zandbergen
G
G
Verhagen
N A
NA
Klar-Mohamad
N
N
Daha
M R
MR
van Kooten
C
C
D000818:Animals; D015703:Antigens, CD / Q000032:analysis*; D015153:Blotting, Western; D002478:Cells, Cultured / Q000276:immunology / Q000378:metabolism; D005920:Glomerular Mesangium / Q000737:chemistry* / Q000166:cytology; D005922:Glomerulonephritis, IGA / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D051381:Rats; D011961:Receptors, Fc / Q000032:analysis*; D012016:Reference Values; D013154:Spleen / Q000737:chemistry
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D015850:Interleukin-6; D012333:RNA, Messenger; D011961:Receptors, Fc