02206nas a2200253   4500000000100000008004100001260001300042653001200055653002500067653002100092653003000113653001100143653002100154653001800175653001600193653002200209100001300231700001100244245007400255300001100329490000700340520159100347022001401938       1998                            d  c1998 Jul10aAnimals10aBacterial Infections10aCarrier Proteins10aCation Transport Proteins10aHumans10aImmunity, Innate10aLeishmaniasis10aMacrophages10aMembrane Proteins1 aGovoni G1 aGros P00aMacrophage NRAMP1 and its role in resistance to microbial infections.  a277-840 v473 a<p>The identification and characterization of genetic factors influencing natural susceptibility to infectious diseases in humans and in model organisms, such as the laboratory mouse, can provide new insight into the basic mechanisms of host defense against infections. In the mouse, resistance or susceptibility to infection with intracellular pathogens such as Salmonella, Mycobacterium and Leishmnania is controlled by the Natural resistance associated macrophage protein (Nramp1) gene on chromosome 1, which influences the rate of intracellular replication of these parasites in macrophages. Nramp1 codes for an integral membrane protein, which is expressed exclusively in macrophage/monocytes and polymorphonuclear leukocytes. The protein is localized to the endosomal/lysosomal compartment of the macrophage and is rapidly recruited to the membrane of the particle-containing phagosome upon phagocytosis. Nramp defines a novel family of functionally related membrane proteins including Nramp2, which was recently shown to be the major transferrin-independent uptake system of the intestine in mammals. This observation supports the hypothesis that the phagocyte-specific Nramp1 protein may regulate the intraphagosomal replication of antigenically unrelated bacteria by controlling divalent cation concentrations at that site. Recent genetic studies have found that allelic variants at the human NRAMP1 locus are associated with susceptibility to leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis) and possibly with the onset of rheumatoid arthritis.</p>  a1023-3830