IgA from HIV+ haemophilic patients triggers intracellular signals coupled to the cholinergic system of the intestine.
IgA was obtained from HIV-infected haemophilic patients and the intracellular signals triggered by its reaction with isolated rat intestinal strips were studied. HIV+ IgA stained intestinal microvilli with a granular immunofluorescence pattern and bound to the muscarinic acetylcholine receptor (mAChR), displacing the specific muscarinic cholinergic antagonist QNB in a non-competitive manner. It triggered the signals that are the consequence of mAChR stimulation in the intestine. Thus, it decreased cAMP synthesis and increased guanosine 3':5'-cyclic monophosphate (cGMP) formation and phosphoinositide (PI) turnover of the intestine. In addition, it stimulated prostaglandin E2(PGE2) synthesis by intestinal strips. Through its effect on PGE2 synthesis, HIV+ IgA could have a dual action. On the one hand, it could enhance immunosuppression at a local level, favouring pathogen growth and subsequent intestinal dysfunction. On the other hand, PGE2 could directly increase intestinal motility and electrolyte/fluid loss. Both effects could be involved in intestinal damage in AIDS.
Sales
M E
ME
CEFYBO-CONICET and School of Dentistry, University of Buenos Aires, Argentina.
Sterin-Borda
L
L
de Bracco
M M
MM
Rodriguez
M
M
Narbaitz
M
M
Borda
E
E
D000818:Animals; D017615:Enteric Nervous System / Q000276:immunology*; D015658:HIV Infections / Q000150:complications / Q000276:immunology*; D006467:Hemophilia A / Q000150:complications / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology* / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D011976:Receptors, Muscarinic / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
D007070:Immunoglobulin A; D011976:Receptors, Muscarinic