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Substance P receptor antagonist reverses intestinal pathophysiological alterations occurring in a novel ex‐vivo model of Cryptosporidium parvum infection of intestinal tissues derived from SIV‐infected macaques
Author(s) -
Garza A.,
Lackner A.,
Aye P.,
D’Souza M.,
Martin P.,
Borda J.,
Tweardy D.J.,
Weinstock J.,
Griffiths J.,
Robinson P.
Publication year - 2008
Publication title -
journal of medical primatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.31
H-Index - 42
eISSN - 1600-0684
pISSN - 0047-2565
DOI - 10.1111/j.1600-0684.2007.00251.x
Subject(s) - ex vivo , cryptosporidium parvum , cryptosporidium , biology , in vivo , simian immunodeficiency virus , pathogenesis , immunology , virology , microbiology and biotechnology , immune system , feces
Background Cryptosporidium infection leads to life‐threatening diarrhea in AIDS patients. Pathogenesis of cryptosporidiosis is due to intestinal physiological alterations. We devised an ex‐vivo model using ex‐vivo Cryptosporidium parvum infection of jejunal tissues derived from SIV‐infected macaques and studied the role of substance P (SP) in the pathogenesis of cryptosporidiosis. Methods We measured jejunal SP protein levels using ELISA, and electrophysiological alterations using the Ussing chamber technique in an ex vivo model of Cryptosporidium infection. Paraformaldehyde‐fixed jejunum from SIV‐infected macaques with and without naturally occurring cryptosporidiosis was studied for SP protein expression by immunohistochemistry and fluorescence deconvolution microscopy. Results Ex‐vivo Cryptosporidium ‐infected tissues and tissues from SIV‐infected macaques with naturally occurring cryptosporidiosis demonstrated elevated SP protein levels compared with tissues from SIV‐infected animals without ex‐vivo C. parvum infection or tissues from SIV‐infected animals that have no evidence of cryptosporidiosis. In our ex‐vivo model of Cryptosporidium infection, we demonstrated pathophysiological alterations that were blocked by SP‐receptor antagonist treatment. Conclusions These studies suggest that SP‐receptor antagonists could prove useful for treatment of AIDS‐related cryptosporidiosis.