Biomedical subjects

Max D Cooper

Publications and source records attributed to Max D Cooper.

41 records · Page 3Linked to original sources

PubMed2002

Exploring lymphocyte differentiation pathways.

Highlights in a 4-decade exploration of lymphocyte differentiation begin with comparative studies in birds and mammals leading to recognition of the separate T- and B-cell differentiation pathways and their cooperative interaction. The global effects of aborting IgM B-cell development with anti-mu antibodies indicated that B cells can undergo immunoglobulin isotype switching. A search for the mammalian bursa equivalent that began with an extended excursion through the gut-associated lymphoepithelial tissues ultimately led to the hematopoietic tissue origin of mammalian B cells. The identification of the precursors of B cells in hematopoietic tissues provided an expanded view of the life history of B cells. A recurring theme in this essay is the interplay between understanding normal lymphocyte differentiation and the defects that underlie immunodeficiency diseases and lymphoid malignancies.

Allergy and Immunology↗

PubMed2002

Fc receptor homologs: newest members of a remarkably diverse Fc receptor gene family.

Newfound relatives of the classical Fc receptors (FcR) have been provisionally named the Fc receptor homologs (FcRH). The recent identification of eight human and six mouse FcRH genes substantially increases the size and functional potential of the FcR family. The extended family of FcR and FcRH genes spans approximately 15 Mb of the human chromosome 1q21-23 region, whereas in mice this family is split between chromosomes 1 and 3. The FcRH genes encode molecules with variable combinations of five subtypes of immunoglobulin (Ig) domains. The presence of a conserved sequence motif in one Ig domain subtype implies Ig Fc binding capability for many FcRH family members that are preferentially expressed by B lineage cells. In addition, most FcRH family members have consensus tyrosine-based activating and inhibitory motifs in their cytoplasmic domains, while the others lack features typical of transmembrane receptors. The FcRH family members, like the classical FcRs, come in multiple isoforms and allelic variations. The unique individual and polymorphic properties of the FcR/FcRH members indicate a remarkably diverse Fc receptor gene family with immunoregulatory function.

Amino Acid Sequence↗

PubMed2002

Definition of an Fc receptor-related gene (FcRX) expressed in human and mouse B cells.

The recent identification of five human Fc receptor (FcR) homologs, hFcRH1-5, has extended the known FcR family and identified an unanticipated richness of the chromosome 1q region in genes encoding potential Ig-binding proteins. In a database search for additional relatives of this family we identified expressed sequence tag representatives of a new FcR-related molecule (hFcRX) and its mouse ortholog (mFcRX). The FcRX cDNAs were cloned from human lymph node and mouse spleen cDNA libraries. hFcRX is located centromeric of FcgammaRII and FcgammaRIII at 1q23, and its mouse ortholog resides in a syntenic region of chromosome 1. The genes encode proteins with 67% interspecies identity that lack both N-linked glycosylation sites and transmembrane regions. Two of the four FcRX domains are Ig-like, and share characteristics similar to FcgammaRI domains 2 and 3, having 28% overall extracellular identity with hFcgammaRI and 27% identity with mFcgammaRI respectively. FcRX transcripts are found primarily in secondary lymphoid tissues, where they are expressed by B lineage cells. FcRX thus may function as a secreted or intracellular protein in normal and neoplastic B cells.

Amino Acid Sequence↗

PubMed2002

Mast cell regulation via paired immunoglobulin-like receptor PIR-B.

Activating (PIR-A) and inhibitory (PIR-B) isoforms of the paired immunoglobulin (Ig)-like receptor family have been evaluated for their modulating potential in mast cell responses to IgE antibody and mast/stem cell growth factor (SCF). Mast cells produce PIR-A and PIR-B, but PIR-B was found to be predominantly expressed on the cell surface, where it was constitutively tyrosine phosphorylated and associated with SHP-1 tyrosine phosphatase. Efficient coligation of PIR-B with FcepsilonRI inhibited IgE-induced mast cell activation and serotonin release. PIR-B and c-kit (or mast/SCF receptor) coligation also inhibited SCF-induced mast cell responses. The PIR-B inhibitory activity was unimpaired in SHP-1-deficient mast cells, perhaps because of non-SHP-1-binding tyrosine-based inhibitory motif in the cytoplasmic tail of PIR-B. This analysis suggests that PIR-B may serve to control mast cell activity.

Animals↗

PubMedDate not supplied

Hypertension and angiotensin II hypersensitivity in aminopeptidase A-deficient mice.

Local concentrations of the vasopressor peptide, angiotensin II (AngII), depend upon the balance between synthesis and degradation. Previous studies of blood pressure (BP) regulation have focused primarily on the generation of AngII and its receptors, and less attention has been devoted to angiotensin degradation. Aminopeptidase A (APA, EC 3.4.11.7) is responsible for the N-terminal cleavage of AngII, a hydrolytic event that serves as a rate-limiting step in angiotensin degradation. To evaluate the physiological role of APA, we examined BP homeostasis in APA-deficient mice. We measured basal BP and BP with continuous infusion of AngII in APA mutant mice by tail-cuff method. We also evaluated the development and histology of AngII-targeted organs as well as urine excretion in these mice. Homozygous APA mutant mice were found to have elevated basal systolic BP when compared with heterozygous mutant and wild-type littermate mice. Infusion of AngII led to an enhanced systolic BP response in the APA-deficient mice. Despite the sustained elevation of BP in APA knockout mice, neither their renal and cardiac sizes nor their histological appearances were not different from control mice. Moreover, the volume, osmolality, and electrolyte content of the urine were normal in APA-deficient mice. APA deficiency increased baseline BP and enhanced the hypertensive response to increased levels of AngII. These findings indicate a physiological role for APA in lowering BP and offer novel insight into the mechanisms for developing hypertension.

Aminopeptidases↗