A Novel Role of Complement Components C1q and C5a in Hematopoietic Stem/Progenitor Cell Migration.
Bibliographic record
Abstract
Abstract The complement protein C1q primarily provides a recognition and activation signal that triggers the classical pathway of complement, but it also has multiple immune functions including acting as a chemoattractant for neutrophils, eosinophils, mast and monocyte-derived dendritic cells. Moreover, hematopoietic stem cells have recently been shown to express the C1q receptor, C1qRp. C5a also strongly chemoattracts monocyte/macrophages to inflammatory sites. Recently we showed that G-CSF mobilization activates complement by a classical IgM-dependent pathway (Blood2005;106:1976a). In this study we examined the possible roles of C1q and C5a in hematopoietic stem/progenitor cells (HSPC) migration. We found that C5aR was expressed at the mRNA level on mobilized peripheral blood (mPB) and cord blood (CB) CD34+ cells but at the protein level only on mPB CD34+ cells. Flow cytometry revealed high C1qRp expression on both mPB and CB CD34+ cells. When the expression of C5aR and C1qRp was examined on the CB CD34+ cells expanded towards myeloid, megakaryocytic and erythroid lineages (at days 0, 3, 6, 11 and 14 of expansion), we found that C5aR expression increased with cell maturation (days 3–14) in both myeloid and megakaryocytic progenitors. In contrast, C1qRp was highly expressed on day 0, stayed constant in myeloid and megakaryocytic cells (days 3–11), and was down-regulated by day 14 in megakaryocytic cells. C1qRp was down-regulated in erythroid precursors during their maturation. We also found that C5a but not C1q is a chemoattractant for mPB CD34+ cells. In chemotaxis assays towards an SDF-1 gradient, C5a primed chemotactic responses of both mPB and CB CD34+ cells to a low (10 ng/mL) gradient of SDF-1 (up to 80% of their response to a high (200 ng/mL) SDF-1 gradient); C1q primed the chemotactic responses of both types of CD34+ cells (up to 100% of the response to a high SDF-1 gradient), and the priming effect of C1q on SDF-1-induced chemotaxis of expanded myeloid and megakaryocytic precursors decreased, consistent with down-regulation of C1qRp on these cells by day 14. Hence these results indicate that HSPC and progenitor cells express functional C5a and C1q receptors and that both the C5a-C5aR and C1q-C1qRp axes sensitize the responses of these cells to SDF-1 and thus could play a role in HSPC homing/mobilization to bone marrow. Further studies in animal models are needed to elucidate the roles of C5a and C1q in HSPC trafficking.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".