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Abnormal chemokine-induced responses of immature and mature hematopoietic cells from motheaten mice implicate the protein tyrosine phosphatase SHP-1 in chemokine responses.

Kim CH, Qu CK, Hangoc G, Cooper S, Anzai N, Feng GS, Broxmeyer HE - J. Exp. Med. (1999)

Bottom Line: These altered chemokine responses did not appear to be due to enhanced expression of CXCR4 or lack of chemokine receptor expression.However, expression of some chemokine receptors (CCR1, CCR2, CCR3, and CXCR2) was significantly enhanced in me(v)/me(v) T cells.Our results implicate SHP-1 involvement in a number of different chemokine-induced biological activities.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

ABSTRACT
Chemokines regulate a number of biological processes, including trafficking of diverse leukocytes and proliferation of myeloid progenitor cells. SHP-1 (Src homology 2 domain tyrosine phosphatase 1), a phosphotyrosine phosphatase, is considered an important regulator of signaling for a number of cytokine receptors. Since specific tyrosine phosphorylation of proteins is important for biological activities induced by chemokines, we examined the role of SHP-1 in functions of chemokines using viable motheaten (me(v)/me(v)) mice that were deficient in SHP-1. Chemotactic responses to stromal call-derived factor 1 (SDF-1), a CXC chemokine, were enhanced with bone marrow myeloid progenitor cells as well as macrophages, T cells, and B cells from me(v)/me(v) versus wild-type (+/+) mice. SDF-1-dependent actin polymerization and activation of mitogen-activated protein kinases were also greater in me(v)/me(v) versus +/+ cells. In contrast, immature subsets of me(v)/me(v) bone marrow myeloid progenitors were resistant to effects of a number of chemokines that suppressed proliferation of +/+ progenitors. These altered chemokine responses did not appear to be due to enhanced expression of CXCR4 or lack of chemokine receptor expression. However, expression of some chemokine receptors (CCR1, CCR2, CCR3, and CXCR2) was significantly enhanced in me(v)/me(v) T cells. Our results implicate SHP-1 involvement in a number of different chemokine-induced biological activities.

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Enhanced chemotaxis of mev/mev myeloid progenitors to SDF-1. Bone marrow myeloid progenitor cells (CFU-GM, progenitors of granulocytes and macrophages) were examined for their ability to transmigrate from the upper chamber towards SDF-1 at indicated concentrations in the lower chamber. After chemotaxis, myeloid progenitors in input and progenitors migrating to the lower chamber were assayed by methylcellulose colony assay. CFU-GM migration was normalized for the number of input CFU-GM to obtain CFU-GM migration rate (% of input ± SD). *Significant differences were observed between +/+ and mev/mev cells (P < 0.05). Results are from one experiment representative of five independent experiments.
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Figure 1: Enhanced chemotaxis of mev/mev myeloid progenitors to SDF-1. Bone marrow myeloid progenitor cells (CFU-GM, progenitors of granulocytes and macrophages) were examined for their ability to transmigrate from the upper chamber towards SDF-1 at indicated concentrations in the lower chamber. After chemotaxis, myeloid progenitors in input and progenitors migrating to the lower chamber were assayed by methylcellulose colony assay. CFU-GM migration was normalized for the number of input CFU-GM to obtain CFU-GM migration rate (% of input ± SD). *Significant differences were observed between +/+ and mev/mev cells (P < 0.05). Results are from one experiment representative of five independent experiments.

Mentions: SDF-1, expressed ubiquitously in many organs including bone marrow and lymphoid tissues, induces chemotaxis of HPCs. It has been suggested that SDF-1 is a chemoattractant that induces the homing and retaining of progenitor cells in bone marrow 1129. Thus far, SDF-1 is the only chemokine shown to induce chemotaxis of early stage myeloid and lymphoid progenitors. We examined the chemotactic responsiveness of CFU-GM (progenitor cells for granulocytes and macrophages) in bone marrow of mev/mev mice and +/+ littermates. The background migration of CFU-GM in +/+ mice and mev/mev mice was very low (Fig. 1). In response to SDF-1, a typical bell-shaped chemotactic response was observed for +/+ progenitors (Fig. 1). Bone marrow CFU-GM from mev/mev mice demonstrated a much higher chemotaxis rate (>50%) than their +/+ counterparts (slightly >10%). Also, mev/mev progenitors began to migrate at lower concentrations of SDF-1 than +/+ progenitors, demonstrating an increased sensitivity of mev/mev CFU-GM to the chemotactic effect of SDF-1.


Abnormal chemokine-induced responses of immature and mature hematopoietic cells from motheaten mice implicate the protein tyrosine phosphatase SHP-1 in chemokine responses.

Kim CH, Qu CK, Hangoc G, Cooper S, Anzai N, Feng GS, Broxmeyer HE - J. Exp. Med. (1999)

Enhanced chemotaxis of mev/mev myeloid progenitors to SDF-1. Bone marrow myeloid progenitor cells (CFU-GM, progenitors of granulocytes and macrophages) were examined for their ability to transmigrate from the upper chamber towards SDF-1 at indicated concentrations in the lower chamber. After chemotaxis, myeloid progenitors in input and progenitors migrating to the lower chamber were assayed by methylcellulose colony assay. CFU-GM migration was normalized for the number of input CFU-GM to obtain CFU-GM migration rate (% of input ± SD). *Significant differences were observed between +/+ and mev/mev cells (P < 0.05). Results are from one experiment representative of five independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2195618&req=5

Figure 1: Enhanced chemotaxis of mev/mev myeloid progenitors to SDF-1. Bone marrow myeloid progenitor cells (CFU-GM, progenitors of granulocytes and macrophages) were examined for their ability to transmigrate from the upper chamber towards SDF-1 at indicated concentrations in the lower chamber. After chemotaxis, myeloid progenitors in input and progenitors migrating to the lower chamber were assayed by methylcellulose colony assay. CFU-GM migration was normalized for the number of input CFU-GM to obtain CFU-GM migration rate (% of input ± SD). *Significant differences were observed between +/+ and mev/mev cells (P < 0.05). Results are from one experiment representative of five independent experiments.
Mentions: SDF-1, expressed ubiquitously in many organs including bone marrow and lymphoid tissues, induces chemotaxis of HPCs. It has been suggested that SDF-1 is a chemoattractant that induces the homing and retaining of progenitor cells in bone marrow 1129. Thus far, SDF-1 is the only chemokine shown to induce chemotaxis of early stage myeloid and lymphoid progenitors. We examined the chemotactic responsiveness of CFU-GM (progenitor cells for granulocytes and macrophages) in bone marrow of mev/mev mice and +/+ littermates. The background migration of CFU-GM in +/+ mice and mev/mev mice was very low (Fig. 1). In response to SDF-1, a typical bell-shaped chemotactic response was observed for +/+ progenitors (Fig. 1). Bone marrow CFU-GM from mev/mev mice demonstrated a much higher chemotaxis rate (>50%) than their +/+ counterparts (slightly >10%). Also, mev/mev progenitors began to migrate at lower concentrations of SDF-1 than +/+ progenitors, demonstrating an increased sensitivity of mev/mev CFU-GM to the chemotactic effect of SDF-1.

Bottom Line: These altered chemokine responses did not appear to be due to enhanced expression of CXCR4 or lack of chemokine receptor expression.However, expression of some chemokine receptors (CCR1, CCR2, CCR3, and CXCR2) was significantly enhanced in me(v)/me(v) T cells.Our results implicate SHP-1 involvement in a number of different chemokine-induced biological activities.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology/Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

ABSTRACT
Chemokines regulate a number of biological processes, including trafficking of diverse leukocytes and proliferation of myeloid progenitor cells. SHP-1 (Src homology 2 domain tyrosine phosphatase 1), a phosphotyrosine phosphatase, is considered an important regulator of signaling for a number of cytokine receptors. Since specific tyrosine phosphorylation of proteins is important for biological activities induced by chemokines, we examined the role of SHP-1 in functions of chemokines using viable motheaten (me(v)/me(v)) mice that were deficient in SHP-1. Chemotactic responses to stromal call-derived factor 1 (SDF-1), a CXC chemokine, were enhanced with bone marrow myeloid progenitor cells as well as macrophages, T cells, and B cells from me(v)/me(v) versus wild-type (+/+) mice. SDF-1-dependent actin polymerization and activation of mitogen-activated protein kinases were also greater in me(v)/me(v) versus +/+ cells. In contrast, immature subsets of me(v)/me(v) bone marrow myeloid progenitors were resistant to effects of a number of chemokines that suppressed proliferation of +/+ progenitors. These altered chemokine responses did not appear to be due to enhanced expression of CXCR4 or lack of chemokine receptor expression. However, expression of some chemokine receptors (CCR1, CCR2, CCR3, and CXCR2) was significantly enhanced in me(v)/me(v) T cells. Our results implicate SHP-1 involvement in a number of different chemokine-induced biological activities.

Show MeSH
Related in: MedlinePlus