Biomedical subjects

A Humbles

Publications and source records attributed to A Humbles.

3 recordsLinked to original sources

PubMed2001

Macrophage inflammatory protein-1alpha uses a novel receptor for primitive hemopoietic cell inhibition.

Macrophage inflammatory protein-1alpha (MIP-1alpha) is a member of the chemokine family of proinflammatory mediators. In addition to its inflammatory roles, MIP-1alpha has been shown to be active as an inhibitor of primitive hemopoietic cell proliferation. Indeed, a dysfunction in this inhibitory process has been postulated to contribute to leukemogenesis. Research has been aimed at characterizing the receptor involved in cellular inhibition by MIP-1alpha. This study demonstrates that of all the beta-chemokines tested, only MIP-1alpha is capable of inhibiting primitive hemopoietic cell proliferation. Because no MIP-1alpha-specific receptors have been identified, this suggests that inhibition is mediated by an uncharacterized receptor. Further evidence for the involvement of a novel receptor in this process is the equivalent potencies of MIP-1alphaS and MIP-1alphaP variants of human MIP-1alpha and the fact that primitive cells from bone marrow derived from individual MIP-1alpha receptor null mice display a full response to MIP-1alpha inhibition.

Animals↗

PubMed2000

Lymph node trafficking and antigen presentation by endobronchial eosinophils.

Because eosinophils recruited into the airways in allergic diseases are exposed to inhaled allergens, we evaluated whether eosinophils within the endobronchial lumen can function in vivo as antigen-presenting cells for inhaled antigens. We recovered eosinophils from the airways after aerosol antigen challenge in sensitized mice or from the peritoneal cavities of IL-5 transgenic mice and fluorescently labeled these cells ex vivo. These labeled cells, instilled intratracheally into normal mice, migrated into draining paratracheal lymph nodes and localized to T cell-rich paracortical areas. The homing of airway eosinophils to lymph nodes was not governed by eotaxin, because CCR3(-/-) and CCR3(+/+) eosinophils migrated identically. Airway eosinophils, recovered after inhalational antigen challenge in sensitized mice, expressed MHC class II and costimulatory CD80 and CD86 proteins and functioned in vitro as CD80- and CD86-dependent, antigen-specific, antigen-presenting cells. Moreover, when instilled into the airways of antigen-sensitized recipient mice, airway eosinophils recovered after inhalational antigen challenge stimulated antigen-specific CD4(+) T cell proliferation within paratracheal lymph nodes. Thus, eosinophils within the lumina of airways can process inhaled antigens, traffic to regional lymph nodes, and function in vivo as antigen-presenting cells to stimulate responses of CD4(+) T cells.

Animals↗

PubMed1999

Structure and function of the murine chemokine receptor CXCR3.

The gene encoding the murine homologue of human CXCR3 exists in a single copy consisting of two exons with an intron interrupting the coding sequence between nucleotides 10 and 11. The deduced amino acid sequence is 86% identical to the predicted human sequence. Murine CXCR3 mRNA is detectable in bone marrow cells cultured in the presence of IL-2 but not unstimulated cells. It is also detectable at low abundance in normal mouse spleen, lymph node, mammary gland, and thymus. Transfection of murine CXCR3 in murine pre-B lymphocyte line (CXCR3++/L1.2) conferred binding of the ligands IP10, ITAC and Mig with K(D)'s of 1.35 +/- 0.56, 1.41 +/- 0.20, and 11.65 +/- 0.90 nM, respectively. Lower affinity binding was observed for several beta or CC chemokines (eotaxin, MCP-3, MIP3alpha and SLC/6Ckine/Exodus 2). ITAC, IP10 and Mig induced chemotaxis with an order of potency ITAC > IP10 = Mig. The chemokines also increased intracellular calcium concentration and were variably desensitized to repeated agonist stimulation. The hierarchy for cross- desensitization was ITAC > Mig > IP10. Thus, while Mig, ITAC and IP10 all act on the same receptor for binding and agonist stimulation, they may interact with different receptor conformational isoforms to produce divergent responses.

Amino Acid Sequence↗