Inhibitory antibodies

Stability studies (holding Circular dichroism spectroscopy quantify drug and antidrug. Neutralizing antibodies (inhibitory effect in bioassay)... 

Takei S, Arora YK, Walker SM. Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens. J Clin Invest. 1993 91 602-607. 

Waxman DJ, Lapenson DP, Park SS, Attisano C, Gel-boin HV (1987) Monoclonal antibodies inhibitory to... 

It is interesting that the stimulus compounds used in the study differ widely in their molecular structures, and yet they all interact with antibodies to thaumatin. It is, therefore, probable that a single receptor-structure responds to all sweet stimuli,there being a variation in the relative effectiveness of sweet stimuli across individual nerve-fibers, and the characteristics of all receptor sites do not appear to be identical. Earlier elec-trophysiological studies of single primary, afferent taste-neurons uniformly agreed that individual fibers very often have multiple sensitivities, and that individual, gustatory receptors are part of the receptive field of more than one afferent fiber. " We have yet to learn how these interact, and the nature of their excitatory, or possible inhibitory, relations, or both. 

Caco-2 cells and ezetimibe, a potent inhibitor of chloresterol absorption in humans, it was reported that (1) carotenoid transport was inhibited by ezetimibe up to 50% and the extent of that inhibition diminished with increasing polarity of the carotenoid molecule, (2) the inhibitory effects of ezetimibe and the antibody against SR-BI on P-carotene transport were additive, and (3) ezetimibe may interact physically with cholesterol transporters as previously suggested - and also down-regulate the gene expression of three surface receptors, SR-BI, NPCILI, and ABCAl. 

The powerful inhibition of Ca " transport without inhibition of ATPase activity seen with polyclonal anti-ATPase sera in earlier studies [305] was probably due to complement dependent lesion of the membrane that permitted the leakage of accumulated calcium [306-308], The scarcity of inhibitory antibodies may imply that the active site of the Ca - ATPase is either inaccessible to antibodies or poorly antigenic, perhaps due to a unique secondary structure. 

According to Mata et al, [309], solubilization in Ci2Eg solution unmasked the inhibitory effect of several antibodies (B/3D6, Y/1F4, Y/2EG, Y/3G6, B/4H3, A/4H3 and I/2H7) on the Ca -ATPase, They suggested that these antibodies bind to protein-protein contact sites opened by the dissociation of ATPase oligomers, thus causing inhibition. Alternatively, the binding of antibody to the solubilized ATPase may promote its folding into a conformation that is unfavorable for enzymatic activity. 

Pruijt JF, Fibbe WE, Laterveer L, et al. Prevention of interleukin-8-induced mobilization of hematopoietic progenitor cells in rhesus monkeys by inhibitory antibodies against the metalloproteinase gelatinase B (MMP-9). Proc Natl Acad Sci USA 1999 96(19) 10863-10868. 

The first study was conducted to determine whether carotenoids and cholesterol share common pathways (transporters) for their intestinal absorption (During et al., 2005). Differentiated Caco-2 cells on membranes were incubated (16 h) with a carotenoid (1 pmol/L) with or without ezetimibe (EZ Zetia, an inhibitor of cholesterol transport), and with or without antibodies against the receptors, cluster determinant 36 (CD36) and scavenger receptor class B, type I (SR-BI). Carotenoid transport in Caco-2 cells (cellular uptake + secretion) was decreased by EZ (lOmg/L) as follows P-C and a-C (50% inhibition) P-cryptoxanthin and LYC (20%) LUT ZEA (1 1) (7%). EZ reduced cholesterol transport by 31%, but not retinol transport. P-Carotene transport was also inhibited by anti-SR-BI, but not by anti-CD36. The inhibitory effects of EZ and anti-SR-BI on P-C transport... 

Corticosteroids also exert inhibitory effects on the overall immune process. These drugs impair the function of the leukocytes responsible for antibody production and destruction of foreign cells. As a result, corticosteroids are also used therapeutically in the prevention of organ transplant rejection. 

Finally, addition of Tyv-specific antibodies to Caco-2 cultures significantly inhibits larval moulting (McVay et al., 2000). It seems likely that the inhibitory effect is an indirect result of antibody-mediated encumbrance of larvae in the monolayer rather than a direct effect on the process of moulting. Nevertheless, the observation provides further support for the conclusion that antibodies specific for Tyv interfere with the niche of the parasite. 

This was the original hypothesis put forward by Lee (1970) and expanded by Ogilvie et al. (1973). Secretory products of N. brasiliensis do indeed decrease the amplitude of contractions of segments of uninfected rat intestine maintained in an organ bath, but a role for AChE in this phenomenon was discounted due to the heat stability of the parasite factor, and the inability to duplicate the effect with AChE from the electric eel (Foster et al., 1994). Subsequent investigations demonstrated that the suppression of contraction could be duplicated by a 30-50 kDa fraction of secreted products, which contained a protein of 30 kDa that was immunologically cross-reactive with mammalian vasoactive intestinal peptide (VIP). Moreover, an antibody to porcine VIP significantly reduced the inhibitory effect of parasite-secreted products on contraction in vitro (Foster and Lee, 1996). 

Another type of intestinal peptide transporter, hPTl, which is significantly different in sequence from PEPT1, was identified using a functionally inhibitory monoclonal antibody [99]. This transporter is widely expressed in the human GI tract and facilitates the oral absorption of pdactam antibiotics and ACE inhibitors from the intestine [18, 99]. Interestingly, we recently reported that hPTl gene expression is approximately 4-fold higher than PEPT1 in the human duodenum [4] (Fig. 11.1). 

IFN-y also directly modulates the immune response by affecting growth, differentiation and function of both T- and B-lymphocytes. These effects are quite complex and are often influenced by additional cytokines. IFN-y acts as a growth factor in an autocrine manner for some T cell sub-populations, and it is capable of suppressing growth of other T cell types. It appears to have an inhibitory effect on development of immature B-lymphocyte populations, but it may support mature B cell survival. It can both up-regulate and down-regulate antibody production under various circumstances. 

Buffo, A., Zagrebelsky, M., Huber, A. B. et al. Application of neutralizing antibodies against NI-35/250 myelin-associated neurite growth inhibitory proteins to the adult rat cerebellum induces sprouting of uninjured Purkinje cell axons. /. Neurosci. 20 2275-2286, 2000. 

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