title: Signaling proteins are represented in tissue fluid/lymph from soft tissues of normal human legs at concentrations different from serum.
abstract: BACKGROUND
  The mobile intercellular fluid flowing to and in the lymphatics contains filtered plasma products and substances synthesized and excreted by tissue cells. Among them are signaling proteins such as cytokines, chemokines, enzymes, and growth factors. They act locally in autocrine and paracrine systems regulating cell metabolism, proliferation, and formation of the ground matrix. They play an immunoregulatory role in infections, wound healing, and tumor cell growth.
  
  
  RESULTS
  In this study we measured the concentration of selected cytokines, chemokines, tissue enzymes, and growth factors in tissue fluid/lymph drained from normal human leg soft tissues. Legs exposed to infections and trauma often result in development of lymphedema. Lymph was drained from superficial calf lymphatics using microsurgical techniques. Our studies showed generally higher concentrations of cytokines, chemokines, enzymes, and growth factors in lymph than in serum. The total protein L/S ratio was 0.22, whereas that of various lymph signaling proteins ranged between 1 and 10.
  
  
  CONCLUSIONS
  This indicates that in addition to proteins filtered from blood, local cells contribute to lymph concentration by own production, depending on the actual cell requirement. Moreover, there were major individual differences of lymph levels with simultaneous stable serum levels. This suggests existence of a local autonomous regulatory humoral mechanism in tissues, not reflected in serum.
authors.affiliation: 1 Department of Surgical Research, Transplantation and Epigenetics, Medical Research Center , Polish Academy of Sciences, Warsaw, Poland .
authors.forename: Marzanna
authors.initials: M
authors.lastname: Zaleska
authors.forename: Waldemar L
authors.initials: WL
authors.lastname: Olszewski
authors.forename: Marek
authors.initials: M
authors.lastname: Durlik
authors.forename: Norman E
authors.initials: NE
authors.lastname: Miller
mesh_terms: D016207:Cytokines / Q000378:metabolism*; D064368:Healthy Volunteers; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007866:Leg / Q000098:blood supply; D008196:Lymph / Q000737:chemistry / Q000378:metabolism*; D042601:Lymphatic Vessels / Q000098:blood supply / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D044967:Serum; D015398:Signal Transduction / Q000502:physiology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9