African-European differences in the capacity of T-cell cytokine production.

Regional differences in immune responsiveness have been studied by comparing the frequency of cytokine producing T cells in healthy African children and adults and their age-matched European counterparts. By use of flow cytometry for the intracellular detection of cytokines an overall expansion of CD4+ and CD8+ T cells producing the Type 1 cytokines interleukin (IL)-2 and interferon (IFN)-gamma was observed in adults when compared with children, giving credit to the cumulative effect of contacts with environmental antigens. The CD4+ cells expressing the Type 2 cytokines IL-4 and IL-13, however, increased only in Africans, probably reflecting continuously present challenges with antigens that preferentially drive Type 2 responses. A striking increased frequency of both Type 1 and Type 2 cytokines producing T cells was found in African adults when compared with their European counterparts. The quantitative and qualitative regional differences in immune reactivity are likely to be of significance for all immune intervention strategies, especially for the design of vaccines.

Prostaglandin E(1) does not influence plasmatic coagulation, hepatic synthesis, or postoperative blood loss in patients after coronary-artery bypass grafting.

STUDY OBJECTIVE: To assess whether postoperatively administered prostaglandin E1 (PGE1) might prevent bleeding in patients after coronary artery bypass grafting (CABG). DESIGN: Prospective, randomized, placebo-controlled trial. SETTING: University-affiliated hospital. PATIENTS: 49 patients scheduled for elective CABG surgery. INTERVENTIONS: The PGE1 group received intravenous PGE(1) up to 15 ng/kg/min for 72 hours after surgery, whereas the placebo group received isotonic saline for the same time period. MEASUREMENTS AND MAIN RESULTS: Nine patients (4 in the PGE1 group vs. 5 in the placebo group) had to be excluded because of hemodynamic instability, and 1 in the placebo group because of gastric bleeding. In the remaining 39 patients (20 vs. 19), no significant differences with regard to hemoglobin levels or platelet count could be observed. There was no significant difference between the groups concerning the amount of packed red blood cells, platelet concentrates, or fresh frozen plasma transfused. No significant differences could be observed regarding laboratory markers of coagulation activation or hepatic synthesis either. CONCLUSIONS: PGE1 did not prevent coagulation disturbances and blood loss when administered postoperatively in patients undergoing CABG. The absence of these expected effects might be explained by the concomitant administration of acetylsalicylic acid, whose antiaggregatory acivity seems to exceed the effects of PGE1.

Relation of pro- and anti-inflammatory cytokines and the production of nitric oxide in patients receiving high-dose immunotherapy with interleukin-2.

Immunotherapy with intravenous recombinant human interleukin-2 (rh IL-2) may be accompanied by hypotension and the emergence of capillary leak syndrome. Nitric oxide (NO) is supposed to be responsible for both side effects. The aim of the current investigation was to elucidate the relationship between pro- and anti-inflammatory cytokines and the production of NO in eight tumor patients receiving intravenous rh IL-2 continuously over a time period of 120 hours. Markers of systemic inflammation, as well as nitrate plasma levels, were consecutively determined. Significant changes in the levels of pro-inflammatory cytokines IL-6 and IL-8 were observed (p < 0.05). In contrast to the anti-inflammatory cytokine IL-10, which did not increase significantly, the serum concentrations of the soluble tumor necrosis factor receptors (sTNFr) I and II rose continuously and significantly during the observation period (p < 0.05). In parallel, a significant rise in nitrate plasma levels was observed (p < 0.05). Moreover, there were highly significant correlations between nitrate and IL-6 serum levels (p < 0.05), nitrate and sTNFr-I (p < 0.05), nitrate and sTNFr-II (p < 0.05), and between IL-6 and IL-10 (p < 0.05), respectively. We conclude that immunotherapy with IL-2 promotes a pro-inflammatory state, parallelled by an increased production of nitric oxide. Although anti-inflammatory responses accompany this process, they are not able to diminish the production of nitric oxide.

Outcome and prognostic factors in critically ill cancer patients admitted to the intensive care unit.

OBJECTIVE: To assess survival in cancer patients admitted to an intensive care unit (ICU) with respect to the nature of malignancy, cause of ICU admittance, and course during ICU stay as well as to evaluate the prognostic value of the Acute Physiology and Chronic Health Evaluation (APACHE) III score. DESIGN: Retrospective cohort study. SETTING: ICU at a university cancer referral center. PATIENTS: A total of 414 cancer patients admitted to the ICU during a period of 66 months. INTERVENTIONS: None. MEASUREMENTS: Charts of the patients were analyzed with respect to underlying disease, cause of admission, APACHE III score, need and duration of mechanical ventilation, neutropenia and development of septic shock, as well as ICU survival and survival after discharge. Mortality data were compared with two control groups: 1362 patients admitted to our ICU suffering from diseases other than cancer and 2,776 cancer patients not admitted to the ICU. MAIN RESULTS: ICU survival was 53%, and 1-yr survival was 23%. The 1-yr mortality rate was significantly lower in both control groups. Patients admitted after bone marrow transplantation had the highest mortality. In a multivariate analysis, prognosis was negatively influenced by respiratory insufficiency, the need of mechanical ventilation, and development of septic shock during the ICU stay. Admission after cardiopulmonary resuscitation yielded high ICU mortality but a relatively good long-term prognosis. Admission after surgery and as a result of acute hemorrhage was associated with a good prognosis. Age, neutropenia, and underlying disease did not influence outcome significantly. Admission APACHE III scores were significantly higher in nonsurvivors but failed to predict individual outcome satisfactorily. All patients with APACHE III scores of >80 died at the ICU. CONCLUSION: A combination of factors must be taken into account to estimate a critically ill cancer patient's prognosis in the ICU. The APACHE III scoring system alone should not be used to make decisions about therapy prolongation. Admission to the ICU worsens the prognosis of a cancer patient substantially; however, as ICU mortality is 47%, comparable with severely ill noncancer patients, general reluctance to admit cancer patients to an ICU does not seem to be justified.

Transient increase in mitogen-induced lymphoproliferative responses in patients with testicular cancer after BEP chemotherapy.

OBJECTIVES: To investigate the impact of polychemotherapy on cellular immunity in patients with testicular cancer. METHODS: Lymphocyte subpopulations, lymphoproliferative responses to mitogenic stimulation, and mitogen-induced release of soluble interleukin-2 receptor from peripheral blood mononuclear cells were investigated in 15 patients with testicular germ cell tumors a median of 61 months (range 7 to 73) after polychemotherapy with bleomycin, etoposide, and cisplatin (BEP). RESULTS: The numbers of peripheral blood T cells (CD3+), CD4+ and CD8+ subsets, and lymphoproliferative responses to pokeweed mitogen, phytohemagglutinin, and concanavalin A in patients were comparable to those of healthy control subjects. When two groups of patients were formed according to elapsed time from BEP polychemotherapy and study onset (group A, 12 months and group B, 69 months after termination of BEP), a significant increase in lymphoproliferative response to concanavalin A (P <0.05) was found in group A 1 year after chemotherapy. CONCLUSIONS: BEP chemotherapy administered to patients with testicular cancer does not result in impairment of cellular immunity but rather leads to a significant increase in the capacity of patients' lymphocytes to respond to mitogenic stimulation up to 1 year after polychemotherapy. Moreover, the increased T-cell activity found after BEP therapy may contribute to the high rate of long-term complete remission.

High prevalence of hyperhomocysteinemia in critically ill patients.

OBJECTIVE: To test the hypothesis that the prevalence of hyperhomocysteinemia is increased in critically ill patients and correlates with disease severity and mortality in these patients. DESIGN: A prospective study. SETTING: Three medical intensive care units at the University of vienna Medical School serving both medical and surgical patients. PATIENTS: All consecutive admissions (n = 56) during a period of 4 wks. A total of 112 age- and gender-matched healthy individuals constituted the control group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were drawn within 24 hrs after admission for analysis of total homocysteine (tHcy), folate, vitamin B6 levels, and vitamin B12 levels as well as to identify the 677C-->T polymorphism in the gene coding for the enzyme 5,10-methylenetetrahydrofolate reductase. Acute Physiology and Chronic Health Evaluation III scores at admission and 24 hrs after admission as well as 30-day survival were documented in all patients. Hyperhomocysteinemia was more prevalent in critically ill patients (16.1%; 95% confidence interval, 7.6% to 28.3%) compared with age- and gender-matched healthy individuals (5.4%; 95% confidence interval, 2.0% to 11.3%; chi-square test; p = .022). There was no difference in tHcy plasma concentrations in the first 24 hrs after admission to an intensive care unit between survivors and nonsurvivors. The 5,10-methylenetetrahydrofolate reductase 677C-->T polymorphism had no influence on tHcy levels and survival of intensive care unit patients. CONCLUSIONS: The prevalence of hyperhomocysteinemia is increased in critically ill patients compared to age- and gender-matched healthy individuals. The clinical significance of this finding remains to be determined.

Experiences with severe P. falciparum malaria in the intensive care unit.

OBJECTIVE: To review the clinical profiles and therapies instituted for patients with severe malaria admitted to an ICU. DESIGN: Retrospective study. SETTING: Internal ICU of a tertiary care centre. PATIENTS AND PARTICIPANTS: Between January, 1992, and February, 1999, 104 patients with malaria were admitted to the General Hospital of Vienna. Sixty-nine patients suffered from Plasmodium falciparum malaria (66%), seven of these were admitted to the ICU. MEASUREMENT AND RESULTS: Seven patients were admitted to the ICU, of whom three died (4% in hospital case-fatality rate). Four patients required mechanical ventilation because of respiratory insufficiency and adult respiratory distress syndrome (ARDS), of whom three died. Three patients were treated with inhaled nitric oxide (NO) and kinetic therapy; one patient required extracorporeal veno-venous oxygenation. All patients who died required haemofiltration because of acute renal failure. CONCLUSION: As P. falciparum is a potentially life-threatening disease, reliable criteria for ICU admission should be defined and risk factors identified. Early ICU monitoring should be attempted, especially under the following conditions: (1) lack of clinical response to anti-malarial treatment within 48 h and/or (2) any signs of neurological disturbance (hypoglycaemia excluded). Prospective multicentre trials and guidelines for supportive intensive care are urgently needed.

Comparison of conventional surgical versus Seldinger technique emergency cricothyrotomy performed by inexperienced clinicians.

BACKGROUND: Cricothyrotomy is the ultimate option for a patient with a life-threatening airway problem. METHODS: The authors compared the first-time performance of surgical (group 1) versus Seldinger technique (group 2) cricothyrotomy in cadavers. Intensive care unit physicians (n = 20) performed each procedure on two adult human cadavers. Methods were compared with regard to ease of use and anatomy of the neck of the cadaver. Times to location of the cricothyroid membrane, to tracheal puncture, and to the first ventilation were recorded. Each participant was allowed only one attempt per procedure. A pathologist dissected the neck of each patient and assessed correctness of position of the tube and any injury inflicted. Subjective assessment of technique and cadaver on a visual analog scale from 1 (easiest) to 5 (worst) was conducted by the performer. RESULTS: Age, height, and weight of the cadavers were not different. Subjective assessment of both methods (2.2 in group 1 vs. 2.4 in group 2) and anatomy of the cadavers (2.2 in group 1 vs. 2.4 in group 2) showed no statistically significant difference between both groups. Tracheal placement of the tube was achieved in 70% (n = 14) in group 1 versus 60% (n = 12) in group 2 (P value not significant). Five attempts in group 2 had to be aborted because of kinking of the guide wire. Time intervals (mean +/- SD) were from start to location of the cricothyroid membrane 7 +/- 9 s (group 1) versus 8 +/- 7s (group 2), to tracheal puncture 46 +/- 37s (group 1) versus 30 +/- 28s (group 2), and to first ventilation 102 +/- 42s (group 1) versus 100 +/- 46s (group 2) (P value not significant). CONCLUSIONS: The two methods showed equally poor performance.

Homocysteine and laminin are not prognostic markers in patients with septic inflammatory response syndrome.

The aim of this study was to measure plasma homocysteine and laminin concentrations in patients with nonbacteremic systemic inflammatory response syndrome (SIRS) and to compare them with those of a healthy control group. Concerning laminin, significant increased concentrations could be observed in the SIRS group compared to the control group, but for homocysteine, no significance could be observed. In summary, homocysteine and laminin levels are not useful in the prediction of a patient's outcome.

Time course of immunological markers in patients with the systemic inflammatory response syndrome: evaluation of sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and TGF-beta 2.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) is viewed as a system-wide inflammatory response. Up until now, no parameter has been available for predicting the development of septic shock. In the present study, we evaluated the usefulness of serum levels of CD14, vascular cells adhesion molecule-1 (VCAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), macrophage inflammatory protein (MIP) 1 alpha and transforming growth factor beta 2 (TGF-beta 2) as early markers of outcome in patients with SIRS. METHODS: A group of 28 SIRS patients (13 survivors/15 non-survivors) was compared with a healthy control group and with patients with local inflammation. Blood samples were analysed on days 0, 4 and 7. Proinflammatory parameters such as sCD14, sVCAM-1, sELAM-1, MIP-1 alpha and anti-inflammatory parameters such as TGF-beta 2 were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: At the beginning, all evaluated proinflammatory immunological parameters with the exception of sVCAM-1 were significantly increased in patients with SIRS compared with the healthy control group. However, no significant difference could be observed for all immunological parameters comparing survivors and non-survivors, with the exception of interleukin (IL) 6 at day 7. CONCLUSION: All evaluated proinflammatory parameters were increased in patients with SIRS during the course of the disease. However, the parameters have no correlation with outcome and prognosis of SIRS patients.

Prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis.

The aim of the present study was to evaluate the potential prognostic value of MIP-1 alpha, TGF-beta 2, sELAM-1, and sVCAM-1 in patients with gram-positive sepsis. Twenty-eight patients with gram-positive sepsis were compared to 11 patients with gram-negative sepsis and 15 healthy volunteers. Sepsis was defined by the criteria of Bone et al. (Crit. Care Med. 21, 5447-5463, 1993) and by isolation of at least two positive blood cultures with gram-positive/gram-negative bacteria. Plasma samples for determination of the immunological parameters were collected daily. Analysis of cytokines and adhesion molecules was performed on days 0 (day of sepsis criteria fulfillment), 4, and 7 (or 1 day before death). In the gram-positive group 10 of 28 patients died; in the gram-negative group 4 of 11 died. Only sELAM-1 plasma concentrations were found to be a useful early parameter in predicting patients' outcome in gram-positive sepsis. sELAM-1 concentrations at the onset of the study (day 0) were significantly higher in the nonsurviving patients than those in the survivors. MIP-1 alpha levels were significantly higher only on days 4 and 7. With regard to the measured plasma concentrations we believe that MIP-1 alpha is not a useful parameter for predicting patients' prognosis. The increase of sVCAM-1 might play a role in the pathogenesis of gram-positive sepsis; however, it could not be relied upon as an early prognostic parameter. The potential role of TGF-beta 2 in the development of gram-positive sepsis could not evaluated in the present study, whereas routine measurements of TGF-beta 2 offered no additional prognostic information.

Is there a place for 2-CDA in the treatment of B-CLL?

There is no doubt about 2-CDA being a very potent lymphotoxic agent that displays high efficacy in the treatment of CLL. It interferes with the intranuclear machinery of DNA regulation, and causes death to proliferative active, as well as resting lymphocytes. Interruption of crucial pathways that are evident for cell survival translates into high clinical response rates in CLL. CR and PR rates comparable to those reported on fludarabine are achieved in relapsed or refractory CLL. Even though trials on previously untreated CLL are still ongoing, a consistent trend towards durable, high CR rates becomes apparent. The toxicity is comparable to that of fludarabine and consists of infections, as well as thrombocytopenia. Clinical as well as in vitro studies suggest a crossresistance between the two purine analogues, indicating that sequential treatment is not useful. Given these data, although preliminary in case of de novo CLL, 2-CDA has to be recognized as one of the most effective cytostatic drugs currently available for CLL treatment. Large prospective trials (in comparison with fludarabine) will assess the role of 2-CDA as standard treatment. Such trials should also have the aim to substantiate the potential of 2-CDA as induction treatment followed by high-dose consolidation.

Activated naive CD4+ peripheral blood T cells in autoimmune thyroid disease.

To better understand the clinical significance of changes in lymphocytes in thyroid disease this study analyzed the proportion of CD19+, CD3+, CD4+ and CD8+ cells among circulating lymphocytes in Graves' disease (GD, n = 34) and autoimmune hypothyroidism (AH, n = 28) vs healthy subjects (n = 15). In addition, the expression of CD25 and CD45 isoforms on CD4+ T cells as well as their modulation by methimazole in patients with GD was measured using three color flow cytometry. It was observed that, irrespective of age, both patients with GD (17.6 +/- 7.0% +/- SD) and those with AH (19.0 +/- 9.5%) had an increased percentage of the CD25+CD45RA+ (naive) subpopulation of helper cells vs healthy subjects (7.9 +/- 2.3%, p < 0.0001). In patients with AH peripheral memory cells and hence overall CD25+ cells were more frequent among helper cells (56.7 +/- 12.2%) than in healthy subjects (40.8 +/- 14.0%, p < 0.001). Patients with GD (46.2 +/- 13.4%) did not differ from normal subjects in this respect. Treatment of GD with MMI reduced the percentage of CD25+CD45RA+ cells among CD4+ cells toward values seen in healthy subjects. In addition, we confirm previous reports that CD8+ cells toward values seen in healthy subjects. In addition, we confirm previous reports that CD8+ cells are significantly reduced in AH (23.9 +/- 4.9%) and untreated Graves' disease (23.2 +/- 6.6%) vs healthy subjects (32.2 +/- 5.9%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of type I-interferons on human thyroid epithelial cells derived from normal and tumour tissue.

Long term interferon (IFN) therapy is frequently associated with side effects which affect the thyroid gland such as hypothyroidism and thyroiditis. We have therefore tested the ability of type I-IFNs to exert direct effects on primary cultures of human thyroid epithelial cells: (i) Type I-IFNs (IFN-alpha 2b and IFN-omega) inhibit cell proliferation as determined by [3H]thymidine incorporation with a half-maximal effect at approximately 1 ng/ml (50 pM). Inhibition of cell growth is observed in cells derived from normal thyroid as well as neoplastic tissue (autonomous and non-secreting adenoma; follicular, papillary and anaplastic carcinoma). (ii) Over a similar concentration range, type I-IFNs suppressed thyroglobulin release by thyroid cells. (iii) IFN-alpha 2b stimulated surface expression of major histocompatibility class (MHC) I but not MHC II molecules, while IFN-gamma enhanced the expression of both MHC I and MHC II molecules. This effect of IFN-gamma, but not that of IFN-alpha 2b was antagonized by suramin. (iv) Incubation of thyroid cells with IFN-alpha 2b also resulted in increased cell surface levels of the intercellular adhesion molecule 1 (ICAM-1). These findings demonstrate that type I-IFNs directly affect thyroid function and explain related side effects of these cytokines. In addition, our results provide a rational basis for the possible use of type I-IFNs in the treatment of patients with advanced thyroid cancer for whom no therapeutic alternative exists.

[Immunohistochemical studies of mononuclear cellular infiltrates of papillary, follicular and anaplastic thyroid cancers]. / Immunohistochemische Untersuchungen des mononukleären zellulären Infiltrates von papillären, follikulären und anaplastischen Schilddrüsenkarzinomen.

The mononuclear cellular infiltrate of thyroid neoplasms was examined by immunohistochemical techniques and compared to normal thyroid (control 1) and untreated Graves' disease tissue (control 2). Using a panel of monoclonal antibodies T-, B cells and macrophage antigens as well as the expression of activation-associated antigens and of MHC class II molecules were examined. In comparison to control 1 an increase of positive cells could be detected in carcinomas. This increase was significant for CD3+ and CD8+ T cells, for CD4+ macrophages and for HLA-DP+ cells in all types of carcinomas. In addition, in anaplastic carcinomas a significant increase of B cells, RM3/1+ macrophages, IL-2R+, ICAM-1+ and HLA-DQ+ cells was observed as well as of HLA-DR+ cells in follicular and of CD4+ T cells in papillary carcinomas. A comparison with control 2 revealed a significant increase of CD4+ cells (T cells and macrophages) in papillary and of CD8+ and RM3/1+ cells in anaplastic carcinomas. Our findings, an obvious increase of cell populations and of an upregulated expression of activation-associated antigens on these cells, indicated an immunological reaction caused by neoplastic thyrocytes. Further functional studies are however necessary.

[Chronic lymphatic leukemia]. / Chronisch lymphatische Leukämie.

Chronic lymphocytic leukemia of the B-cell type (B-CLL) is the most common type of leukemia. The diagnosis is based on the demonstration of sustained lymphocytosis, bone marrow lymphocytosis and the presence of CD 19/CD5 positive cells. The most important prognostic factor is the stage of the disease (according to RAI or BINET) and the lymphocyte doubling time. Most early stage patients do not benefit from chemotherapy and, indeed, some of these patients never require treatment. Stage A patients with active disease and stage B patients are treated conventionally with chlorambucil/prednisone, but the optimum dosage and duration of chlorambcil treatment has not yet been established. In stage C patients anthracycline containing regimens appear to be more effective. The nucleoside analogues fludarabine and 2-chlorodeoxyadenosine (cladribine) have been shown to be active in patients refractory to alkylating agents. Their role in primary treatment is currently being evaluated in ongoing studies. For a small proportion of patients with advanced disease aged less than 55 years allogeneic or autologous bone marrow transplantation offers the chance of long term remission and possibly even cure, which never can be achieved with conventional chemotherapy.

T-T cell interactions in patients with endocrine autoimmunity. Definition of antiergotypic T lymphocytes.

T-T cell interactions are known to be of importance in the generation of immune responses and have been postulated to play a role in autoimmunity. Antiergotypic T lymphocytes are cells, which react with other activated T cells, which they may consecutively neutralize. Antiergotypic T cells have been described to play a role in animal models of autoimmunity and have been found in patients with rheumatoid arthritis. It was the aim of the present study to analyse, whether antiergotypic T cells were also present in the blood of patients with endocrine autoimmunity and to characterize them in vitro. We found that peripheral blood mononuclear cells from patients with Graves' disease, Hashimoto's thyroiditis and Diabetes mellitus show a pronounced proliferative response, when stimulated with autologous T cell lines. This response is dependent on the state of activation of the stimulator cell population, but is independent of its phenotype and is not MHC restricted. In contrast to normal control cells PBMC from patients with endocrine autoimmune disorders respond better to autologous T lymphocytes, than to allogeneic T cells and to autologous E- monocytic cells. T cells responsive to activated autologous T cell lines can also be expanded from PBMC. They may be CD4+ or CD8+ and recognize autologous T cells in the presence of autologous PBMC as feeder cells. These results suggest the presence of a T-T cell network in patients with endocrine autoimmune disease, which may have an important regulatory role in the disease process.

Monocytes do not make mast cells when cultured in the presence of SCF. Characterization of the circulating mast cell progenitor as a c-kit+, CD34+, Ly-, CD14-, CD17-, colony-forming cell.

Mast cells (MC3) belong to the hemopoietic system and arise from hemopoietic precursor cells. Human MC progenitors can be detected in the bone marrow as well as in the peripheral blood (pb) and are responsive to the mast cell growth factor SCF, the ligand of the c-kit tyrosine kinase receptor. However, little is known about the subsets of cells that become committed to and differentiate into mature human MC. In this study, the identity of the circulating MC progenitor, previously felt to be a monocyte (Mo) or basophil (Ba), was investigated. For this purpose, CD14+ pb monocytes, CD17+ pb basophils and CD34+ cord blood cells were purified to homogeneity (> 95%) from mononuclear cells (normal adult donors, n = 17, cord blood, n = 2) by counter-flow centrifugation followed by cell sorting with mAb. In the presence of rhSCF, MC developed in long term suspension culture from pure CD34+ cells but not from pure Mo, pure Ba, or Ly (MC-tryptase levels on day 42: CD14+ Mo: 3.7 +/- 0.8 vs CD17+ Ba: 3.2 +/- 0.5 vs Ly: 2.0 +/- 1.5 vs control: 196.5 +/- 92.5 ng/ml, p < 0.001). Depletion of CD34+ cells from MNC resulted in a loss of MC in long term suspension culture, whereas depletion of either Mo, Ba, or Ly did not. In methyl-cellulose cultures in the presence of rhSCF, MC and tryptase could be detected in pure (CFU-mast) and mixed (CFU-myeloid/mast) MC colonies. Together, MC do not originate from circulating Mo, Ba, or Ly. The circulating MC progenitor is a CD34+, c-kit+, Ly-, CD14-, CD17- colony-forming cell. This is the first definitive demonstration that mast cells are replenished directly from early hemopoietic progenitors and thus form a unique cell lineage within the hemopoietic system.