Fibrocytes are circulating, hematopoietic cells that express CD45 and Col1a1. They contribute to wound healing and several fibrosing disorders by mechanisms that are poorly understood. In this report, we demonstrate that fibrocytes predispose the lung to B16-F10 metastasis by recruiting Ly-6C+ monocytes. To do so, we isolated fibrocytes expressing CD45, CD11b, CD13, and Col1a1 from the lungs of wild type (WT) and Ccr5−/− mice. WT but not Ccr5−/− fibrocytes increased the number of metastatic foci when injected into Ccr5−/− mice (73 ± 2 versus 32 ± 5; p < 0.001). This process was MMP9 dependent. Injection of WT enhanced GFP+ fibrocytes also increased the number of Gr-1Int, CD11b+, and enhanced GFP− monocytes. Like premetastatic-niche monocytes, these recruited cells expressed Ly-6C, CD117, and CD45. The transfer of these cells into Ccr5−/− mice enhanced metastasis (90 ± 8 foci) compared with B cells (27 ± 2), immature dendritic cells (31 ± 6), or alveolar macrophages (28 ± 3; p < 0.05). WT and Ccl2−/− fibrocytes also stimulated Ccl2 expression in the lung by 2.07 ± 0.05- and 2.78 ± 0.36-fold compared with Ccr5−/− fibrocytes (1.0 ± 0.06; p < 0.05). Furthermore, WT fibrocytes did not increase Ly-6C+ monocytes in Ccr2−/− mice and did not promote metastasis in either Ccr2−/− or Ccl2−/− mice. These data support our hypothesis that fibrocytes contribute to premetastatic conditioning by recruiting Ly-6C+ monocytes in a chemokine-dependent process. This work links metastatic risk to conditions that mobilize fibrocytes, such as inflammation and wound repair.

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During the second phase of osteogenesis in vitro, rat osteoblasts secrete inducer(s) of chemotaxis and chemoinvasion of endothelial and tumor cells. We report here the characterization and purification from mature osteoblast conditioned medium of the agent chemotactic for endothelial cells. The chemoactive conditioned medium specifically induces directional migration of endothelial cells, not affecting the expression and activation of gelatinases, cell proliferation, and scattering. Directional migration induced in endothelial cells by conditioned medium from osteoblasts is inhibited by pertussis toxin, by blocking antibodies to integrins ␣ 1 , ␤ 1 , and ␤ 3 , and by antibodies to metalloproteinase 2 and 9. The biologically active purified protein has two sequences, coincident with the amino-terminal amino acids, respectively, of the ␣ 1 and of the ␣ 2 carboxyl propeptides of type I collagen, as physiologically produced by procollagen C proteinase. Antibodies to type I collagen and to the carboxyl terminus of ␣ 1 or ␣ 2 chains inhibit chemotaxis. The chemoattractant is the propeptide trimer carboxyl-terminal to type I collagen, and its activity is lost upon reduction. These data illustrate a previously unknown function for the carboxyl-terminal trimer, possibly relevant in promoting endothelial cell migration and vascularization of tissues producing collagen type I.Vascularization and angiogenesis implicate directional migration of endothelial cells, their proliferation, and morphogenesis of the vessels (1). A number of factors have been shown to be capable of promoting each of these events, and some factors have been shown capable of inducing more than one of them (1-3). Factors involved in regulating angiogenesis act in autocrine and paracrine fashion. The production of chemoattractants by organs and tissues to be vascularized, coupled with the production of morphogenetic and mitogenic factors by these organs and/or the endothelial cells, is the emerging rule for control of vascularization in physiological and pathological circumstances (1-3). During the formation of long bone, there is transformation of the perichondrium around the cartilage model to a periosteum with bone being laid down at the midshaft region. At the outer surface of the cartilage model, near its center, blood vessels invade the calcified cartilage that is eroded, opening up a marrow cavity. Epiphyseal growth cartilages are then established to promote endochondral ossification, and angiogenesis occurs at the growth plate. Vascularization in endochondral ossification of the growth plates has been shown to depend on the function of VEGF 1 (1) and the expression of metalloproteinase-9. Vascularization at the diaphyseal region and formation of bone marrow were not reported to be affected in mice null for these genes. (4, 5).In vitro early passage tibia-derived rat osteoblasts secrete in a developmentally regulated fashion, during the second phase of osteogenesis and coinciding with the highest level of synthesis of type I collagen, substance(s)...

Proinflammatory components are present in abdominal aortic aneurysm (AAA). Circulating monocytes display heterogeneity, and three subsets have been identified, based on the differential expression for CD14 and CD16 receptors: CD14+CD16-, classical, CD14+CD16+, intermediate and CD14dimCD16+, non-classical monocytes. Increased proinflammatory CD16+monocytes with high expression of CD143 are present in CKD patients. D-dimer is increased in AAA patients, and might contribute to the pro-inflammatory response associated to circulating monocytes. We aimed to investigate the frequency of CD14+CD16+, CD14dimCD16+monocytes and monocyte CD143 expression in AAA patients, and their relationship with D-dimer, eGFR and other inflammatory parameters. Blood from 74 AAA patients and 30 healthy controls was analyzed to determine the frequency of CD14+, CD16+, CD14dimCD16+monocytes and the monocyte CD143 expression by means of flow-cytometry. AAA patients had expanded CD16+SUPsets (CD14+CD16+: 7.66 ± 0.31% vs 5.42 ± 0.27%; CD14dimCD16+: 7.43 ± 0.48% vs 5.54 ± 0.38%, AAA vs controls, mean ± SE, both p<0.05). CD14+CD16+cells were associated to D-dimer and age, and to reduced eGFR. CD14dimCD16+cells were associated to uric acid, surface CD143, and reduced count of total leukocytes and neutrophils. Within AAA patients, the two CD16+supsets and the monocyte CD143 expression display different relationships with D-dimer, parameters of renal function and circulating biochemical and inflammatory biomarkers.