Characterization of Fpr-rs8, an atypical member of the mouse formyl peptide receptor gene family.

The formyl peptide receptor gene family encodes G protein-coupled receptors for phagocyte chemoattractants, including bacteria- and mitochondria-derived N-formylpeptides. The human family has 3 functional genes, whereas the mouse family has 7 functional genes and 2 possible pseudogenes (ΨFpr-rs2 and ΨFpr-rs3). Here we characterize ΨFpr-rs2, a duplication of Fpr-rs2.

Enhanced function with decreased internalization of carboxy-terminus truncated CXCR4 responsible for WHIM syndrome.

Objective: WHIM (warts, hypogammaglobulinemia, recurrent bacterial infection, myelokathexis) syndrome is an autosomal dominant immune deficiency with severe chronic neutropenia and marrow neutrophil apoptosis. Carboxy-termini truncating mutations in the chemokine receptor CXCR4 have been identified in WHIM patients. We created a retrovirus encoding mutated CXCR4 (truncating point mutation 1000C-->T [R334X] inherited heterozygously in several WHIM patients) in order to transducer healthy human CD34 stem cells and K562 to overexpress mutated CXCR4 and determined its effect on receptor responses to stromal-derived factor-1 (SDF1).

CXCR4-transgene expression significantly improves marrow engraftment of cultured hematopoietic stem cells.

Hematopoietic stem cells (HSCs) lose marrow reconstitution potential during ex vivo culture. HSC migration to stromal cell-derived factor (SDF)-1 (CXCL12) correlates with CXC chemokine receptor 4 (CXCR4) expression and marrow engraftment. We demonstrate that mobilized human CD34+ peripheral blood stem cells (CD34+ PBSCs) lose CXCR4 expression during prolonged culture.